search
Back to results

Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

Primary Purpose

Adult Primary Cholangiocellular Carcinoma, Advanced Adult Primary Liver Cancer, Cholangiocarcinoma of the Extrahepatic Bile Duct

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cediranib maleate
oxaliplatin
leucovorin calcium
fluorouracil
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Primary Cholangiocellular Carcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with histopathological or cytopathological diagnosis of advanced biliary carcinoma (gallbladder cancer, cholangiocarcinoma, ampullary cancer) not amenable to conventional surgical approach are eligible
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
  • No patients with untreated brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  • Life expectancy of greater than 12 weeks
  • White blood cell (WBC)/leukocytes ≥ 3,000/μL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelets ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 3 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 times institutional upper limit of normal
  • Creatinine within normal institutional limits OR calculated creatinine clearance ≥ 60 mL/min
  • No patients with proteinuria not meeting the criteria below; urine sample must be tested by urine protein:creatinine (UPC) ratio or by urinalysis method within 1 week of starting study treatment; depending upon the testing method used, the following criteria must be met:

    • UPC ratio must be < 1.0; if UPC ratio is ≥ 1.0, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein
    • Urinalysis must indicate 0-1+ protein; if urinalysis reading is ≥ 2+, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use adequate contraception (hormonal or barrier method of birth control; abstinence) before and during study treatment

    • Acceptable contraception includes abstinence, oral contraceptives, intra-uterine device (IUD), diaphragm, Norplant, approved hormone injections, condoms, or documentation of medical sterilization
  • Patients with evidence of heart disease must be New York Heart Association (NYHA) Class I or II

    • NYHA Class II patients controlled with treatment are considered at increased risk for compromised left ventricular ejection fraction (LVEF) and will undergo increased cardiac monitoring
  • No patients with other active invasive cancers except nonmelanoma skin cancer or carcinoma in-situ of the cervix

    • History of prior cancer is allowed as long as there has been no evidence of disease within the past 5 years
  • No patients with mean corrected QT interval (QTc) > 480 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
  • No patients with uncontrolled hypertension defined as systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg, with or without anti-hypertensive medication or history of hypertensive crisis or hypertensive encephalopathy

    • Patients with initial BP elevations are eligible once their BP is controlled to above parameters
  • No patients with uncontrolled intercurrent illness including, but not limited to:

    • Hypertension (> 140/90 mm Hg)
    • Chronic or active infection requiring chronic suppressive antibiotics
    • History of or symptomatic congestive heart failure requiring chronic medical therapy
    • NYHA class III or IV heart disease
    • Unstable angina pectoris within 180 days prior to starting study treatment
    • Myocardial infarction within 180 days prior to study treatment
    • Gastroduodenal ulcer(s) determined by endoscopy to be active within 180 days prior to study treatment
    • Serious or non-healing wound, skin ulcers, or bone fracture
    • Any significant bleeding that is not related to the primary tumor within 180 days prior to study treatment
    • Known bleeding diathesis or coagulopathy
    • Paresthesias, peripheral sensory neuropathy > gr. 1 per Common Terminology Criteria for Adverse Events (CTCAE) v.4, or peripheral motor neuropathy ≥ gr. 2 per CTCAE v.4
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No patients with history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 180 days prior to study treatment, symptomatic peripheral ischemia; history of arterial thrombotic event within 180 days prior to study treatment; gastrointestinal (GI) perforation within 180 days prior to study treatment
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients who are chemotherapy naive unless chemotherapy was given as adjuvant post-surgical treatment and at least 6 months have elapsed since adjuvant chemotherapy
  • No patients who have had major surgical procedures, open biopsies, or significant traumatic injury within 28 days prior to study treatment
  • Chemotherapy for prior cancer is permitted
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator

    • Efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 30 days
  • Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
  • Patients may not be receiving therapeutic doses of Coumadin or equivalent
  • No patients requiring drugs with proarrhythmic potential

Sites / Locations

  • Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
  • Ireland Cancer Center Landerbrook Health Center
  • Lake University Ireland Cancer Center
  • UHHS-Chagrin Highlands Medical Center
  • UH-Seidman Cancer Center at Saint John Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cediranib maleate and modified FOLFOX)

Arm Description

Patients receive cediranib maleate PO QD on days 1-14 and modified FOLFOX6 comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1.

Outcomes

Primary Outcome Measures

The Response Rate of Patients Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
The number of patients with a Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Secondary Outcome Measures

Tabulation of the Toxicity Profile of the Combination Therapy
Number of patients that experienced >/= grade 3 treatment related toxicities (definite, probable, possible).
Progression Free Survival
Time in months that evaluable subjects survived progression free
Estimation of Overall Survival
Time of overall response
Identification of Factors That Predict Survival
Factors that predict survival will be identified by Cox model or extended Cox model.

Full Information

First Posted
October 26, 2010
Last Updated
February 10, 2017
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01229111
Brief Title
Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers
Official Title
A Phase 2 Study of AZD2171 (Cediranib) With Modified FOLFOX6 in Patients With Advanced Biliary Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Lack of Drug Supply
Study Start Date
October 2010 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial is studying how well giving cediranib maleate together with combination chemotherapy works in treating patients with advanced biliary cancers. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cediranib maleate together with combination chemotherapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the response rate to AZD2171 (cediranib maleate) and modified folinic acid-fluorouracil-oxaliplatin-6 regimen (FOLFOX 6) in subjects with advanced biliary cancers. SECONDARY OBJECTIVES: I. To determine overall assessment of toxicity of AZD2171 and modified FOLFOX6. II. To determine the progression-free survival of subjects with advanced biliary cancers treated with AZD2171 and modified FOLFOX6. III. To determine overall survival of subjects with advanced biliary cancers treated with AZD2171 and modified FOLFOX6. OUTLINE: Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-14 and modified FOLFOX6 comprising oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Primary Cholangiocellular Carcinoma, Advanced Adult Primary Liver Cancer, Cholangiocarcinoma of the Extrahepatic Bile Duct, Cholangiocarcinoma of the Gallbladder, Localized Unresectable Adult Primary Liver Cancer, Periampullary Adenocarcinoma, Recurrent Adult Primary Liver Cancer, Recurrent Extrahepatic Bile Duct Cancer, Recurrent Gallbladder Cancer, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cediranib maleate and modified FOLFOX)
Arm Type
Experimental
Arm Description
Patients receive cediranib maleate PO QD on days 1-14 and modified FOLFOX6 comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1.
Intervention Type
Drug
Intervention Name(s)
cediranib maleate
Other Intervention Name(s)
AZD2171, Recentin
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Other Intervention Name(s)
CF, CFR, LV
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-fluorouracil, 5-Fluracil, 5-FU
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
The Response Rate of Patients Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Description
The number of patients with a Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Tabulation of the Toxicity Profile of the Combination Therapy
Description
Number of patients that experienced >/= grade 3 treatment related toxicities (definite, probable, possible).
Time Frame
Up to 3 years
Title
Progression Free Survival
Description
Time in months that evaluable subjects survived progression free
Time Frame
Up to 3 years
Title
Estimation of Overall Survival
Description
Time of overall response
Time Frame
Up to 3 years
Title
Identification of Factors That Predict Survival
Description
Factors that predict survival will be identified by Cox model or extended Cox model.
Time Frame
Up to three years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histopathological or cytopathological diagnosis of advanced biliary carcinoma (gallbladder cancer, cholangiocarcinoma, ampullary cancer) not amenable to conventional surgical approach are eligible Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan No patients with untreated brain metastases Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%) Life expectancy of greater than 12 weeks White blood cell (WBC)/leukocytes ≥ 3,000/μL Absolute neutrophil count ≥ 1,500/μL Platelets ≥ 100,000/μL Hemoglobin ≥ 9 g/dL Total bilirubin ≤ 3 mg/dL Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 times institutional upper limit of normal Creatinine within normal institutional limits OR calculated creatinine clearance ≥ 60 mL/min No patients with proteinuria not meeting the criteria below; urine sample must be tested by urine protein:creatinine (UPC) ratio or by urinalysis method within 1 week of starting study treatment; depending upon the testing method used, the following criteria must be met: UPC ratio must be < 1.0; if UPC ratio is ≥ 1.0, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein Urinalysis must indicate 0-1+ protein; if urinalysis reading is ≥ 2+, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein Not pregnant or nursing Negative pregnancy test Fertile patients must use adequate contraception (hormonal or barrier method of birth control; abstinence) before and during study treatment Acceptable contraception includes abstinence, oral contraceptives, intra-uterine device (IUD), diaphragm, Norplant, approved hormone injections, condoms, or documentation of medical sterilization Patients with evidence of heart disease must be New York Heart Association (NYHA) Class I or II NYHA Class II patients controlled with treatment are considered at increased risk for compromised left ventricular ejection fraction (LVEF) and will undergo increased cardiac monitoring No patients with other active invasive cancers except nonmelanoma skin cancer or carcinoma in-situ of the cervix History of prior cancer is allowed as long as there has been no evidence of disease within the past 5 years No patients with mean corrected QT interval (QTc) > 480 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome No patients with uncontrolled hypertension defined as systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg, with or without anti-hypertensive medication or history of hypertensive crisis or hypertensive encephalopathy Patients with initial BP elevations are eligible once their BP is controlled to above parameters No patients with uncontrolled intercurrent illness including, but not limited to: Hypertension (> 140/90 mm Hg) Chronic or active infection requiring chronic suppressive antibiotics History of or symptomatic congestive heart failure requiring chronic medical therapy NYHA class III or IV heart disease Unstable angina pectoris within 180 days prior to starting study treatment Myocardial infarction within 180 days prior to study treatment Gastroduodenal ulcer(s) determined by endoscopy to be active within 180 days prior to study treatment Serious or non-healing wound, skin ulcers, or bone fracture Any significant bleeding that is not related to the primary tumor within 180 days prior to study treatment Known bleeding diathesis or coagulopathy Paresthesias, peripheral sensory neuropathy > gr. 1 per Common Terminology Criteria for Adverse Events (CTCAE) v.4, or peripheral motor neuropathy ≥ gr. 2 per CTCAE v.4 Psychiatric illness/social situations that would limit compliance with study requirements No patients with history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 180 days prior to study treatment, symptomatic peripheral ischemia; history of arterial thrombotic event within 180 days prior to study treatment; gastrointestinal (GI) perforation within 180 days prior to study treatment Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible Patients who are chemotherapy naive unless chemotherapy was given as adjuvant post-surgical treatment and at least 6 months have elapsed since adjuvant chemotherapy No patients who have had major surgical procedures, open biopsies, or significant traumatic injury within 28 days prior to study treatment Chemotherapy for prior cancer is permitted Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator Efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 30 days Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine) Patients may not be receiving therapeutic doses of Coumadin or equivalent No patients requiring drugs with proarrhythmic potential
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Smitha Krishnamurthi
Organizational Affiliation
Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Ireland Cancer Center Landerbrook Health Center
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Facility Name
Lake University Ireland Cancer Center
City
Mentor
State/Province
Ohio
ZIP/Postal Code
44060
Country
United States
Facility Name
UHHS-Chagrin Highlands Medical Center
City
Orange Village
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
UH-Seidman Cancer Center at Saint John Medical Center
City
Westlake
State/Province
Ohio
ZIP/Postal Code
44145
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

We'll reach out to this number within 24 hrs