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Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002) (AL3818)

Primary Purpose

Endometrial Carcinoma, Ovarian Carcinoma, Fallopian Tube Carcinoma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AL3818
Paclitaxel
Pegylated Liposomal Doxorubicin (PLD)
Topotecan
Topotecan
Carboplatin
Paclitaxel
AL3818
Sponsored by
Advenchen Laboratories, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Carcinoma focused on measuring Dual receptor Tyrosine Kinase Inhibitor, Anti-angiogenic therapy, Combination Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Critera

  1. Female ≥ 18 years of age
  2. Histologically proven diagnosis of:

    a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent Stage I to II endometrial and other uterine cancers, after at least one prior line of standard therapy, requiring further treatment with platinum-based chemotherapy ii. Advanced Stage III to IV endometrial and other uterine cancers requiring treatment with platinum-based chemotherapy

    b. Ovarian Cancer: Platinum-sensitive or platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer treated with at least one prior line of platinum-based chemotherapy and requiring further treatment.(Part 1/Phase Ib, Part 2/Phase 2a)

    Platinum-sensitive is defined as cancer progression ≥ 6 months after platinum- based chemotherapy. Platinum-resistant is defined as cancer progression < 6 months after platinum-based chemotherapy.

    Histologic cell types eligible are endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified.

    Phase III/Part 3:

(1) Platinum-resistant (progression within 6 months after last platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer that meets one of the following criteria: i. Subject has received at least two prior lines of systemic therapy including a bevacizumab-containing regimen as standard of care ii. Subject has received at least two prior lines of systemic therapy, has not received a prior bevacizumab-containing regimen and is not eligible for a bevacizumab containing regimen based on Investigator's assessment (2) Platinum-refractory (progression during first-line platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer after at least one prior line of systemic therapy (3) For groups 1-2 above: Subjects with positive deleterious or suspected deleterious, germline or somatic BRCA mutated status must have received a PARP inhibitor as a prior line of therapy.

c. Cervical cancer: recurrent or metastatic cervical cancer that is not amenable to curative treatment with surgery and/or radiation therapy after at least one prior line of standard therapy, requiring further treatment. Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma

3. Have measureable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment.

4. Life expectancy of ≥ 3 months at the time of enrollment.

5. Able to take orally administered study medication.

6. Have adequate baseline function and performance status within 28 days of enrollment:

  1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3
  2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN) or if creatinine is > 1.5 x ULN, creatinine clearance must be > 50 mL/min.
  3. Hepatic function: bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT ≤ 3.0 × ULN.
  4. Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or PTT < 1.2 x ULN
  5. ECOG performance ≤ 2

    7. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment.

    8. Provide written informed consent and authorization permitting release of Protected Health Information.

    9. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.

Exclusion Criteria

  1. Serious, non-healing wound, ulcer or bone fracture.
  2. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia).
  3. (Intentionally left blank)
  4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
  5. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment.

    a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy.

  6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study.
  7. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease.
  8. Women who are pregnant or nursing.
  9. (Intentionally left blank)
  10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
  11. Hemoptysis within 3 months prior to enrollment.
  12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction.
  13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.
  14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life-threatening medical condition that required it.
  15. Known history of human immunodeficiency virus infection (HIV).
  16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection).
  17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy.
  18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product.
  19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
  20. Intra-abdominal abscess within the last 3 months of enrollment.
  21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP >160 mm Hg or diastolic BP > 90 mm Hg pressure.
  22. QTc > 470 msec on screening ECG per Fridericia's formula.
  23. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  24. Concurrent use of concomitant medications that prolong the QT/QTc interval.
  25. Baseline echocardiogram (within 56 days of enrollment) with left ventricular ejection fraction (LVEF) < 50%.
  26. History of difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption of AL3818.
  27. History of pancreatitis; history of renal disease that includes histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy or other renal insufficiencies.
  28. Treatment with an investigational agent within 28 days of enrollment.
  29. Known recreational substance abuse.
  30. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular weight heparin, or any other anticoagulant may be included provided the subject has been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to enrollment.
  31. Known hypersensitivity to AL3818 or components of the formulation.

Sites / Locations

  • Chao Family Comprehensive Cancer Center|UCI Health
  • The Oncology Institute of Hope and Innovation
  • University of California Los Angeles Health
  • University of Miami Sylvester Comprehensive Cancer Center
  • Baptist Health Lexington Oncology Research
  • LSU Health New Orleans
  • Washington University
  • CHI Health
  • Montefiore Medical Center
  • AHN West Penn Hospital
  • UTSW
  • Providence Southwest Washington
  • University of Wisconsin Madison
  • Henan Cancer Hospital
  • Jilin Cancer Hospital
  • The First Hospital of China Medical University
  • Zhongda Hospital Southeast University
  • Tianjin Central Hospital of Gynecology Obstetrics
  • Obstetrics&Gynecology Hospital of Fudan University
  • Beijing Cancer Hospital
  • Chongqing University Cancer Hospital
  • Weifang People's Hospital
  • National Cancer Institute IRCCS "G. Pascale" Foundation
  • University Hospital of Bologna-IRCCS
  • Romagnolo Institute For the Study of Tumors "Dino Amadori"
  • Cannizzaro Emergency Hospital
  • Complex Structure Gynecology Oncology National Cancer Institute of Milan
  • Operative Unit of Oncology
  • Agostino Gemelli University Hospital Rome
  • Campus Bio Medico University Hospital Foundation
  • Severance HospitalRecruiting
  • Samsung Medical CenterRecruiting
  • Korea University Guro HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Hospital Universitario Reina Sofía
  • Hospital Regional Universitario de Málaga
  • ICO Badalona
  • Hospital Universitari Vall d'Hebrón
  • Hospital Clínico Universitario de Valencia
  • Hospital Clínic de Barcelona
  • Hospital Universitario Ramón y Cajal
  • Hospital Clínico San Carlos
  • HCU Virgen Arrixaca
  • Cambridge University Hospitals NHS Foundation Trust
  • The Royal Marsden NHS Foundation Trust
  • The Christie NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Other

Experimental

Experimental

Arm Label

Phase 3 -Active Treatment Arm

Phase 3-Control Treatment Arm

Phase 1b: AL3818 plus carboplatin and paclitaxel

Phase 2a: AL3818 plus carboplatin and paclitaxel

Arm Description

Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups: Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan) Pegylated liposomal doxorubicin (PLD) Topotecan

Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups: Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan) Pegylated liposomal doxorubicin (PLD) Topotecan

Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.

Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.

Outcomes

Primary Outcome Measures

Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Objective Response Rates (ORR) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. ORR is measured by the number of complete (CR) and partial responses (PR)
Measure the Progression Free Survival (PFS)- Part 3 ( Phase 3)
To evaluate the efficacy between the Active Arm (AL3818 in combination with background chemotherapy) and Control Arm (background chemotherapy alone arm) as measured by the primary endpoint of Progression Free Survival (PFS).

Secondary Outcome Measures

Number of Participants with Adverse Events as a measure of safety and toxicity of 21-Day cycles of AL3818 as measured by incidence and severity of treatment-related adverse events (TRAE) - Part 1 (Phase 1b)
Incidence and severity of treatment-related adverse events reported and their relationship to AL3818 will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.3).
Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. Measured as CR+PR+SD (SD ≥ 16 weeks from inclusion).
Progression-Free Survival (PFS) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. Kaplan-Meier analysis
Overall Survival (OS) - Part 2 (Phase 2a)
Overall survival is defined as the date the study treatment was initiated to the date of death from any cause. Kaplan-Meier analysis
Objective Response Rate- Part 3 ( Phase 3)
To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of objective response rate (ORR). (OS).
Duration Of Response - Part 3 ( Phase 3)
To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of duration of response (DOR)
Overall Survival - Part 3 ( Phase 3)
To evaluate the efficacy between the Active Arm and Control Arm as measured by the endpoints of Overall survival

Full Information

First Posted
August 28, 2015
Last Updated
October 19, 2023
Sponsor
Advenchen Laboratories, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02584478
Brief Title
Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)
Acronym
AL3818
Official Title
A Phase 1/2a/3 Evaluation of the Safety and Efficacy of Adding AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2015 (undefined)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Advenchen Laboratories, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to standard platinum-based chemotherapy concurrently in Subjects with Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma.
Detailed Description
This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818(Anlotinib, INN: Catequentinib) to standard platinum-based chemotherapy concurrently and continued as a maintenance therapy for up to 12 months, in subjects with recurrent or metastatic endometrial, ovarian, fallopian, primary peritoneal, or cervical carcinoma. AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions. Phase 1 & 2: This study is divided into two parts. The objective of Part 1 is the evaluation of the safety and tolerability of adding oral AL3818 to standard carboplatin plus paclitaxel chemotherapy for a cycle of 21 days to determine the recommended Phase II dose (RP2D). Phase 1 / Part 1 is now complete. Part 2-The objective of Part 2 is evaluation of preliminary efficacy and the safety of adding oral AL3818 at the RP2D determined in Part 1 to carboplatin and paclitaxel chemotherapy for 6 cycles. Continuous maintenance mono therapy with 14 days on and 7 days off regimen at the RP2D will be conducted up to 12 months and is extendable beyond until disease progression. Phase I is closed and Phase 2 is closed. Phase 3: This study is currently a Phase III, multi-center, randomized trial with active control designed to evaluate the efficacy and safety of AL3818 8 mg plus background treatment (Active Arm) vs background treatment alone (Control Arm), where three background treatments, weekly paclitaxel, pegylated liposomal doxorubicin (PLD), and topotecan are utilized. Oral AL3818 8 mg may be given concurrently with background treatment or alone if the background treatment must be discontinued due to its toxicity for up to 24 cycles of therapy, in subjects with recurrent or metastatic platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 is open.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Carcinoma, Ovarian Carcinoma, Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma, Cervical Carcinoma
Keywords
Dual receptor Tyrosine Kinase Inhibitor, Anti-angiogenic therapy, Combination Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Overall duration of the study will be approximately 42 months. Part 1 and 2 of this study are not randomized and have no concurrent controls. AL3818 and chemotherapy will be administered in an open-label fashion. Phase III/Part 3 is unblinded and randomized. Within each one of the three background chemotherapy groups, subjects will be randomized at a 1:1 ratio stratified by prior angiogenesis inhibitors mainly Avastin use status (Yes or No) and number of prior treatment (≤3 or >3) to receive AL3818 plus background chemotherapy (Active Arm) or background chemotherapy alone (Control Arm).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
270 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 3 -Active Treatment Arm
Arm Type
Experimental
Arm Description
Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups: Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan) Pegylated liposomal doxorubicin (PLD) Topotecan
Arm Title
Phase 3-Control Treatment Arm
Arm Type
Other
Arm Description
Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups: Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan) Pegylated liposomal doxorubicin (PLD) Topotecan
Arm Title
Phase 1b: AL3818 plus carboplatin and paclitaxel
Arm Type
Experimental
Arm Description
Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.
Arm Title
Phase 2a: AL3818 plus carboplatin and paclitaxel
Arm Type
Experimental
Arm Description
Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.
Intervention Type
Drug
Intervention Name(s)
AL3818
Other Intervention Name(s)
Anlotinib Hydrochloride, Anlotinib, Catequentinib
Intervention Description
Taken daily from Day 8 to Day 21 (14 days),administered orally combination with one background chemotherapy in 21-day cycles.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Weekly single agent Paclitaxel will be administered on Day 1, 8, and 15 of each 21-day cycle. Suggested dose: 80 mg/m^2 intravenously or local standard. Paclitaxel may also be administered once weekly with a 1-week break every 3 weeks in lieu of every week
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin (PLD)
Intervention Description
Single agent Pegylated Liposomal Doxorubicin (PLD) administered every 4 weeks on the following cycle days corresponding with AL3818 cycles until maximum cumulative dose per local standard reached. Suggested dose: 40 mg/m^2 intravenously or local standard
Intervention Type
Drug
Intervention Name(s)
Topotecan
Other Intervention Name(s)
Daily Topotecan
Intervention Description
Daily Topotecan on Days 1-5 of each 21-day cycle Suggested dose: 1.25 mg/m2 intravenously or local standard OR Weekly Topotecan with a 1 week break every 3 weeks. Suggested dose: 4 mg/m2 intravenously or local standard
Intervention Type
Drug
Intervention Name(s)
Topotecan
Other Intervention Name(s)
Weekly Topotecan
Intervention Description
Weekly Topotecan with a 1 week break every 3 weeks Suggested dose: 4 mg/m2 intravenously or local standard
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
AUC 5/6 on Day 1 of each 21-Day cycles
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
175mg/m2 IV over 3 hours on Day 1 of each 21-Day cycle
Intervention Type
Drug
Intervention Name(s)
AL3818
Intervention Description
Taken daily from Day 8 to Day 21 (14 days). Administered orally.
Primary Outcome Measure Information:
Title
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Description
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Time Frame
Cycle 1 (21-days)
Title
Objective Response Rates (ORR) - Part 2 (Phase 2a)
Description
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. ORR is measured by the number of complete (CR) and partial responses (PR)
Time Frame
12 months
Title
Measure the Progression Free Survival (PFS)- Part 3 ( Phase 3)
Description
To evaluate the efficacy between the Active Arm (AL3818 in combination with background chemotherapy) and Control Arm (background chemotherapy alone arm) as measured by the primary endpoint of Progression Free Survival (PFS).
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a measure of safety and toxicity of 21-Day cycles of AL3818 as measured by incidence and severity of treatment-related adverse events (TRAE) - Part 1 (Phase 1b)
Description
Incidence and severity of treatment-related adverse events reported and their relationship to AL3818 will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.3).
Time Frame
Cycle 1 (Day 21)
Title
Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)
Description
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. Measured as CR+PR+SD (SD ≥ 16 weeks from inclusion).
Time Frame
12 Months
Title
Progression-Free Survival (PFS) - Part 2 (Phase 2a)
Description
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles in the first 9 cycles then once every 6 cycles for up to 12 months. Kaplan-Meier analysis
Time Frame
Duration of time from the start of treatment to the time of documented disease progression or death, whichever comes first, followed for 12 months.
Title
Overall Survival (OS) - Part 2 (Phase 2a)
Description
Overall survival is defined as the date the study treatment was initiated to the date of death from any cause. Kaplan-Meier analysis
Time Frame
Cycle 1 Day 1 up to 5 years
Title
Objective Response Rate- Part 3 ( Phase 3)
Description
To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of objective response rate (ORR). (OS).
Time Frame
12 Months
Title
Duration Of Response - Part 3 ( Phase 3)
Description
To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of duration of response (DOR)
Time Frame
12 Months
Title
Overall Survival - Part 3 ( Phase 3)
Description
To evaluate the efficacy between the Active Arm and Control Arm as measured by the endpoints of Overall survival
Time Frame
12 Months
Other Pre-specified Outcome Measures:
Title
Toxicity as assessed by CTCAE (v4.3) - Part 2 (Phase 2a)
Description
Incidence and severity of treatment-related adverse events reported and their relationship to AL3818 will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.3)
Time Frame
12 Months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Critera Female ≥ 18 years of age Histologically proven diagnosis of: a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent Stage I to II endometrial and other uterine cancers, after at least one prior line of standard therapy, requiring further treatment with platinum-based chemotherapy ii. Advanced Stage III to IV endometrial and other uterine cancers requiring treatment with platinum-based chemotherapy b. Ovarian Cancer: Platinum-sensitive or platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer treated with at least one prior line of platinum-based chemotherapy and requiring further treatment.(Part 1/Phase Ib, Part 2/Phase 2a) Platinum-sensitive is defined as cancer progression ≥ 6 months after platinum- based chemotherapy. Platinum-resistant is defined as cancer progression < 6 months after platinum-based chemotherapy. Histologic cell types eligible are endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified. Phase III/Part 3: (1) Platinum-resistant (progression within 6 months after last platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer that meets one of the following criteria: i. Subject has received at least two prior lines of systemic therapy including a bevacizumab-containing regimen as standard of care ii. Subject has received at least two prior lines of systemic therapy, has not received a prior bevacizumab-containing regimen and is not eligible for a bevacizumab containing regimen based on Investigator's assessment (2) Platinum-refractory (progression during first-line platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer after at least one prior line of systemic therapy (3) For groups 1-2 above: Subjects with positive deleterious or suspected deleterious, germline or somatic BRCA mutated status must have received a PARP inhibitor as a prior line of therapy. c. Cervical cancer: recurrent or metastatic cervical cancer that is not amenable to curative treatment with surgery and/or radiation therapy after at least one prior line of standard therapy, requiring further treatment. Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma 3. Have measureable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment. 4. Life expectancy of ≥ 3 months at the time of enrollment. 5. Able to take orally administered study medication. 6. Have adequate baseline function and performance status within 28 days of enrollment: Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3 Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN) or if creatinine is > 1.5 x ULN, creatinine clearance must be > 50 mL/min. Hepatic function: bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT ≤ 3.0 × ULN. Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or PTT < 1.2 x ULN ECOG performance ≤ 2 7. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment. 8. Provide written informed consent and authorization permitting release of Protected Health Information. 9. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures. Exclusion Criteria Serious, non-healing wound, ulcer or bone fracture. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia). (Intentionally left blank) Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment. a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease. Women who are pregnant or nursing. (Intentionally left blank) Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia. Hemoptysis within 3 months prior to enrollment. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life-threatening medical condition that required it. Known history of human immunodeficiency virus infection (HIV). Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection). Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection). Intra-abdominal abscess within the last 3 months of enrollment. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP >160 mm Hg or diastolic BP > 90 mm Hg pressure. QTc > 470 msec on screening ECG per Fridericia's formula. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). Concurrent use of concomitant medications that prolong the QT/QTc interval. Baseline echocardiogram (within 56 days of enrollment) with left ventricular ejection fraction (LVEF) < 50%. History of difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption of AL3818. History of pancreatitis; history of renal disease that includes histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy or other renal insufficiencies. Treatment with an investigational agent within 28 days of enrollment. Known recreational substance abuse. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular weight heparin, or any other anticoagulant may be included provided the subject has been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to enrollment. Known hypersensitivity to AL3818 or components of the formulation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shiying Sprinzl
Phone
805-530-1550
Email
shiyings@advenchen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Director
Organizational Affiliation
Advenchen Laboratories, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Chao Family Comprehensive Cancer Center|UCI Health
City
Irvine
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Withdrawn
Facility Name
The Oncology Institute of Hope and Innovation
City
Long Beach
State/Province
California
ZIP/Postal Code
90805
Country
United States
Individual Site Status
Completed
Facility Name
University of California Los Angeles Health
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Baptist Health Lexington Oncology Research
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
LSU Health New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Individual Site Status
Withdrawn
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
CHI Health
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68102
Country
United States
Individual Site Status
Withdrawn
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
AHN West Penn Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UTSW
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Providence Southwest Washington
City
Lacey
State/Province
Washington
ZIP/Postal Code
98503
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Wisconsin Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Henan Cancer Hospital
City
Hefei
State/Province
Henan
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
Country
China
Individual Site Status
Active, not recruiting
Facility Name
The First Hospital of China Medical University
City
Shenyang
State/Province
Shenyang
ZIP/Postal Code
110001
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Zhongda Hospital Southeast University
City
Chongqing
State/Province
Sichuan
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Tianjin Central Hospital of Gynecology Obstetrics
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Obstetrics&Gynecology Hospital of Fudan University
City
Shanghai
State/Province
Yangpu District
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Beijing Cancer Hospital
City
Beijing
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Chongqing University Cancer Hospital
City
Chongqing
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Weifang People's Hospital
City
Weifang
Country
China
Individual Site Status
Active, not recruiting
Facility Name
National Cancer Institute IRCCS "G. Pascale" Foundation
City
Naples
State/Province
Campania
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
University Hospital of Bologna-IRCCS
City
Bologna
State/Province
Emilia-Romagna
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Romagnolo Institute For the Study of Tumors "Dino Amadori"
City
Meldola (FC)
State/Province
Forlì-Cesena
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Cannizzaro Emergency Hospital
City
Catania
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Complex Structure Gynecology Oncology National Cancer Institute of Milan
City
Milan
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Operative Unit of Oncology
City
Ravenna
ZIP/Postal Code
44266
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Agostino Gemelli University Hospital Rome
City
Rome
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Campus Bio Medico University Hospital Foundation
City
Rome
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Severance Hospital
City
Seoul,
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yujeong study coordinator
Email
yjhuh@yuhs.ac
First Name & Middle Initial & Last Name & Degree
Jungyun Lee, MD
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
05351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeonghee Study coordinator
Email
jeonghee21.an@samsung.com
First Name & Middle Initial & Last Name & Degree
Yoo Young Lee, MD
Facility Name
Korea University Guro Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyungme study coordinator
Email
kyungme0316@gmail.com
First Name & Middle Initial & Last Name & Degree
Hyun-woong Cho, MD
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
YoungHee study coordinator
Email
snu_lottie@snu.ac.kr
First Name & Middle Initial & Last Name & Degree
Hee Seoung Kim, MD
Facility Name
Hospital Universitario Reina Sofía
City
Córdoba
State/Province
Andalucía
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Regional Universitario de Málaga
City
Malaga
State/Province
Andalucía
ZIP/Postal Code
29011
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
ICO Badalona
City
Badalona
State/Province
Catalunya
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitari Vall d'Hebrón
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
State/Province
Comunidad Valenciana
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
HCU Virgen Arrixaca
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
State/Province
Cambridgeshire
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
The Christie NHS Foundation Trust
City
Manchester
Country
United Kingdom
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
15602010
Citation
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80. doi: 10.1124/pr.56.4.3.
Results Reference
background
PubMed Identifier
10690548
Citation
Kondo Y, Arii S, Mori A, Furutani M, Chiba T, Imamura M. Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line. Clin Cancer Res. 2000 Feb;6(2):622-30.
Results Reference
background
PubMed Identifier
17324579
Citation
Roskoski R Jr. Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007 Jun;62(3):179-213. doi: 10.1016/j.critrevonc.2007.01.006. Epub 2007 Feb 26.
Results Reference
background
PubMed Identifier
11250709
Citation
Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. Breast Cancer Res. 2000;2(3):191-6. doi: 10.1186/bcr53. Epub 2000 Mar 25.
Results Reference
background
PubMed Identifier
20595807
Citation
Cole C, Lau S, Backen A, Clamp A, Rushton G, Dive C, Hodgkinson C, McVey R, Kitchener H, Jayson GC. Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer. Cancer Biol Ther. 2010 Sep 1;10(5):495-504. doi: 10.4161/cbt.10.5.12585. Epub 2010 Sep 4.
Results Reference
background
PubMed Identifier
21878941
Citation
Raja FA, Griffin CL, Qian W, Hirte H, Parmar MK, Swart AM, Ledermann JA. Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Br J Cancer. 2011 Sep 27;105(7):884-9. doi: 10.1038/bjc.2011.334. Epub 2011 Aug 30.
Results Reference
background
Citation
Ledermann JA, Perren TJ, Raja FA, et al: Randomized double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum-sensitive ovarian cancer: Results of the ICON6 trial. European Cancer Congress. Abstract 10. Presented September 30, 2013.
Results Reference
background
PubMed Identifier
20426765
Citation
Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010 Aug;11(8):1000-17. doi: 10.2174/138945010791591395.
Results Reference
background
PubMed Identifier
10901370
Citation
Shen GH, Ghazizadeh M, Kawanami O, Shimizu H, Jin E, Araki T, Sugisaki Y. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000 Jul;83(2):196-203. doi: 10.1054/bjoc.2000.1228.
Results Reference
background
PubMed Identifier
10419737
Citation
Chen CA, Cheng WF, Lee CN, Chen TM, Kung CC, Hsieh FJ, Hsieh CY. Serum vascular endothelial growth factor in epithelial ovarian neoplasms: correlation with patient survival. Gynecol Oncol. 1999 Aug;74(2):235-40. doi: 10.1006/gyno.1999.5418.
Results Reference
background
PubMed Identifier
9521169
Citation
Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst. 1998 Mar 18;90(6):447-54. doi: 10.1093/jnci/90.6.447.
Results Reference
background
PubMed Identifier
18024865
Citation
Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007 Nov 20;25(33):5180-6. doi: 10.1200/JCO.2007.12.0782. Erratum In: J Clin Oncol. 2008 Apr 1;26(10):1773.
Results Reference
background
Citation
Burger RA, Brady MF, Bookman MA et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC) or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings. Vol. 28, No 18S, 2010 June 20 suppl: Abstract LBA1
Results Reference
background
PubMed Identifier
22529265
Citation
Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23.
Results Reference
background
PubMed Identifier
12684405
Citation
Yokoyama Y, Charnock-Jones DS, Licence D, Yanaihara A, Hastings JM, Holland CM, Emoto M, Sakamoto A, Sakamoto T, Maruyama H, Sato S, Mizunuma H, Smith SK. Expression of vascular endothelial growth factor (VEGF)-D and its receptor, VEGF receptor 3, as a prognostic factor in endometrial carcinoma. Clin Cancer Res. 2003 Apr;9(4):1361-9.
Results Reference
background
PubMed Identifier
12942123
Citation
Holland CM, Day K, Evans A, Smith SK. Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer. Br J Cancer. 2003 Sep 1;89(5):891-8. doi: 10.1038/sj.bjc.6601194.
Results Reference
background
PubMed Identifier
11745191
Citation
Giatromanolaki A, Sivridis E, Brekken R, Thorpe PE, Anastasiadis P, Gatter KC, Harris AL, Koukourakis MI; Tumour and Angiogenesis Research Group. The angiogenic "vascular endothelial growth factor/flk-1(KDR) receptor" pathway in patients with endometrial carcinoma: prognostic and therapeutic implications. Cancer. 2001 Nov 15;92(10):2569-77. doi: 10.1002/1097-0142(20011115)92:103.0.co;2-3.
Results Reference
background
PubMed Identifier
11328416
Citation
Gornall RJ, Anthony FW, Coombes EJ, Hogston P, Woolas RP. Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement. Int J Gynecol Cancer. 2001 Mar-Apr;11(2):164-6. doi: 10.1046/j.1525-1438.2001.011002164.x.
Results Reference
background
PubMed Identifier
17306350
Citation
McMeekin DS, Sill MW, Benbrook D, Darcy KM, Stearns-Kurosawa DJ, Eaton L, Yamada SD; Gynecologic Oncology Group. A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: a Gynecologic Oncology Group study. Gynecol Oncol. 2007 May;105(2):508-16. doi: 10.1016/j.ygyno.2007.01.019. Epub 2007 Feb 15.
Results Reference
background
PubMed Identifier
15867479
Citation
Talvensaari-Mattila A, Soini Y, Santala M. VEGF and its receptors (flt-1 and KDR/flk-1) as prognostic indicators in endometrial carcinoma. Tumour Biol. 2005 Mar-Apr;26(2):81-7. doi: 10.1159/000085589. Epub 2005 May 3.
Results Reference
background
PubMed Identifier
17295646
Citation
Saito M, Sato Y, Watanabe J, Kuramoto H, Kaba S, Fukuda T. Angiogenic factors in normal endometrium and endometrial adenocarcinoma. Pathol Int. 2007 Mar;57(3):140-7. doi: 10.1111/j.1440-1827.2006.02071.x.
Results Reference
background
PubMed Identifier
11161857
Citation
Hirai M, Nakagawara A, Oosaki T, Hayashi Y, Hirono M, Yoshihara T. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma. Gynecol Oncol. 2001 Feb;80(2):181-8. doi: 10.1006/gyno.2000.6056.
Results Reference
background
PubMed Identifier
16557278
Citation
Giatromanolaki A, Koukourakis MI, Turley H, Sivridis E, Harris AL, Gatter KC; Tumour and Angiogenesis Research Group. Phosphorylated KDR expression in endometrial cancer cells relates to HIF1alpha/VEGF pathway and unfavourable prognosis. Mod Pathol. 2006 May;19(5):701-7. doi: 10.1038/modpathol.3800579.
Results Reference
background
PubMed Identifier
21537039
Citation
Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. doi: 10.1200/JCO.2010.32.6397. Epub 2011 May 2.
Results Reference
background
PubMed Identifier
7563170
Citation
Guidi AJ, Abu-Jawdeh G, Berse B, Jackman RW, Tognazzi K, Dvorak HF, Brown LF. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst. 1995 Aug 16;87(16):1237-45. doi: 10.1093/jnci/87.16.1237.
Results Reference
background
PubMed Identifier
7535719
Citation
Wiggins DL, Granai CO, Steinhoff MM, Calabresi P. Tumor angiogenesis as a prognostic factor in cervical carcinoma. Gynecol Oncol. 1995 Mar;56(3):353-6. doi: 10.1006/gyno.1995.1062.
Results Reference
background
PubMed Identifier
9042271
Citation
Ravazoula P, Zolota V, Hatjicondi O, Sakellaropoulos G, Kourounis G, Maragoudakis ME. Assessment of angiogenesis in human cervical lesions. Anticancer Res. 1996 Nov-Dec;16(6B):3861-4.
Results Reference
background
PubMed Identifier
9345352
Citation
Dellas A, Moch H, Schultheiss E, Feichter G, Almendral AC, Gudat F, Torhorst J. Angiogenesis in cervical neoplasia: microvessel quantitation in precancerous lesions and invasive carcinomas with clinicopathological correlations. Gynecol Oncol. 1997 Oct;67(1):27-33. doi: 10.1006/gyno.1997.4835.
Results Reference
background
Citation
Cella DF. Manual for the Functional Assessment of Cancer Therapy (FACT) Measurement System (version 4). Center for Outcomes, Research and Education (CORE), Northwestern University, Chicago, 1997
Results Reference
background
PubMed Identifier
16647106
Citation
Wright JD, Viviano D, Powell MA, Gibb RK, Mutch DG, Grigsby PW, Rader JS. Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer. Gynecol Oncol. 2006 Nov;103(2):489-93. doi: 10.1016/j.ygyno.2006.03.023. Epub 2006 May 2.
Results Reference
background
Citation
36. Krishnansu Sujata Tewari, Michael Sill, Harry J. Long,et al. Plenary Session, Abstract # 3, J Clin Oncol 31, 2013 (suppl; abstract 3)
Results Reference
background
PubMed Identifier
18299146
Citation
Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T. Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol. 2008 May;109(2):250-4. doi: 10.1016/j.ygyno.2008.01.028. Epub 2008 Mar 4.
Results Reference
background
PubMed Identifier
15904950
Citation
Tinker AV, Bhagat K, Swenerton KD, Hoskins PJ. Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol. 2005 Jul;98(1):54-8. doi: 10.1016/j.ygyno.2005.03.037.
Results Reference
background
PubMed Identifier
12826431
Citation
Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Trope C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. doi: 10.1016/s0140-6736(03)13718-x.
Results Reference
background
Links:
URL
http://www.cdc.gov/cancer/ovarian/statistics/
Description
Ovarian Cancer Statistics, CDC 2014

Learn more about this trial

Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)

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