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Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

Primary Purpose

Brenner Tumor, Fallopian Tube Cancer, Ovarian Clear Cell Cystadenocarcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
adjuvant therapy
paclitaxel
carboplatin
bevacizumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brenner Tumor

Eligibility Criteria

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

Inclusion Criteria: Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer Stage II-IV disease The following histologic epithelial cell types are eligible: Serous adenocarcinoma Mucinous adenocarcinoma Clear cell adenocarcinoma Transitional cell carcinoma Adenocarcinoma not otherwise specified Endometrioid adenocarcinoma Undifferentiated carcinoma Mixed epithelial carcinoma Malignant Brenner's tumor Optimal (≤ 1 cm residual disease) OR suboptimal residual disease after initial debulking surgery (performed within the past 12 weeks) Synchronous primary endometrial cancer OR prior history of endometrial cancer allowed provided all of the following are true: Stage IB disease or less Less than 3 mm invasion without vascular or lymphatic invasion No poorly differentiated subtypes, including the following: Papillary serous Clear cell Other FIGO grade 3 lesions No epithelial tumors of low malignant potential (borderline tumors) No CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases by history or evidence upon physical examination within the past 6 months Performance status - GOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 INR ≤ 1.5 PTT < 1.2 times upper limit of normal (ULN) No active bleeding or pathologic conditions carrying high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels) AST ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN Bilirubin ≤ 1.5 times ULN No acute hepatitis Creatinine ≤ 2.0 mg/dL Urine protein-creatinine ratio < 1.0 OR protein 1.0 g by 24 hour urine collection Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided the patient's cardiac status has been stable for ≥ 6 months before study entry No clinically significant cardiovascular disease, including any of the following: Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg Myocardial infarction or unstable angina within the past 6 months New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Peripheral vascular disease ≥ CTCAE grade 2 (at least brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit) No history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within the past 6 months Not pregnant or nursing Fertile patients must use effective contraception during and for ≥ 6 months after completion of bevacizumab therapy No neuropathy (sensory and motor) > grade 1 No active infection requiring antibiotics No circumstances that would preclude study participation No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies No history of allergic reaction to polysorbate 80 (e.g., etoposide, vitamin E) No other invasive malignancies within the past 5 years except non-melanoma skin cancer or localized breast cancer No serious, non-healing wound, ulcer, or bone fracture No significant traumatic injury within 28 days prior to bevacizumab therapy No prior history of abdominal fistula or gastrointestinal perforation within the past 3-6 months Granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection allowed but require weekly wound examinations No clinical symptoms or signs of gastrointestinal obstruction requiring parenteral hydration and/or nutrition At least 28 days since intra-abdominal abscess and recovered At least 3 years since prior adjuvant chemotherapy for localized breast cancer Patients must remain free of recurrent or metastatic disease At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin Patient must remain free of recurrent or metastatic disease No prior radiotherapy to any portion of the abdominal cavity or pelvis No concurrent amifostine or other protective agents No concurrent major surgical procedure or open biopsy or within 28 days prior to bevacizumab therapy No core biopsy within 7 days prior to bevacizumab therapy No prior therapy for this malignancy No prior cancer treatment that contraindicates study therapy No prior anti-VEGF drug, including bevacizumab

Sites / Locations

  • University of California Medical Center At Irvine-Orange Campus
  • University of Chicago
  • University of Iowa Hospitals and Clinics
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Cooper Hospital University Medical Center
  • Wake Forest University Health Sciences
  • Riverside Methodist Hospital
  • Cancer Care Associates-Midtown
  • Tulsa Cancer Institute
  • Gynecologic Oncology Group
  • Fox Chase Cancer Center
  • Women and Infants Hospital
  • M D Anderson Cancer Center
  • Pacific Gynecology Specialists
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • Seattle Cancer Care Alliance
  • University of Washington Medical Center
  • Kawasaki Medical School
  • Saitama Medical University International Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)

Arm Description

Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of intraperitoneal carboplatin with intravenous paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel at the MTD, assessed by CTCAE v3.0
Number of observed DLTs in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0

Secondary Outcome Measures

Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0
Response rate (in patients with measurable disease who are in the expanded cohort) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
Progression-free survival assessed by RECIST

Full Information

First Posted
March 8, 2004
Last Updated
July 19, 2019
Sponsor
National Cancer Institute (NCI)
Collaborators
Gynecologic Oncology Group
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1. Study Identification

Unique Protocol Identification Number
NCT00079430
Brief Title
Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Official Title
A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of Intraperitoneal Carboplatin (NSC #214240) and Intravenous Paclitaxel (NSC # 673089) and Intravenous Paclitaxel, Intraperitoneal Carboplatin and NCI Supplied Intravenous Bevacizumab (NSC #704865) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
June 2004 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
This phase I trial is studying the side effects and best dose of adjuvant intraperitoneal carboplatin when given together with paclitaxel and bevacizumab in treating patients who have undergone debulking surgery for stage II , stage III, or stage IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are more effective than carboplatin and paclitaxel in treating ovarian epithelial or primary peritoneal cancer, or fallopian tube cancer.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of intraperitoneal carboplatin when administered with paclitaxel during course 1, in patients with stage II-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer who had initial debulking surgery. II. Determine the feasibility of this regimen in these patients. III. Determine the feasibility of adding IV bevacizumab to this regimen in courses 2-6. SECONDARY OBJECTIVES: I. Determine the toxicity profile of this regimen in these patients. II. Determine the toxicity profile of paclitaxel and bevacizumab IV in combination with intraperitoneal carboplatin in these patients. III. Determine the response rate (in patients with measurable disease who are in the expanded cohort) and progression-free survival of patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of intraperitoneal carboplatin. Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 20-40 patients are treated at that dose level. Patients are followed every 3 months for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brenner Tumor, Fallopian Tube Cancer, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mixed Epithelial Carcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Serous Cystadenocarcinoma, Ovarian Undifferentiated Adenocarcinoma, Primary Peritoneal Cavity Cancer, Stage II Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)
Arm Type
Experimental
Arm Description
Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Intervention Description
Given intraperitoneally
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of intraperitoneal carboplatin with intravenous paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Time Frame
3 weeks
Title
Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel at the MTD, assessed by CTCAE v3.0
Time Frame
12 weeks
Title
Number of observed DLTs in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0
Time Frame
12 weeks
Title
Response rate (in patients with measurable disease who are in the expanded cohort) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
Up to 1 year
Title
Progression-free survival assessed by RECIST
Time Frame
From study entry until disease progression, death or date of last contact, up to 1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer Stage II-IV disease The following histologic epithelial cell types are eligible: Serous adenocarcinoma Mucinous adenocarcinoma Clear cell adenocarcinoma Transitional cell carcinoma Adenocarcinoma not otherwise specified Endometrioid adenocarcinoma Undifferentiated carcinoma Mixed epithelial carcinoma Malignant Brenner's tumor Optimal (≤ 1 cm residual disease) OR suboptimal residual disease after initial debulking surgery (performed within the past 12 weeks) Synchronous primary endometrial cancer OR prior history of endometrial cancer allowed provided all of the following are true: Stage IB disease or less Less than 3 mm invasion without vascular or lymphatic invasion No poorly differentiated subtypes, including the following: Papillary serous Clear cell Other FIGO grade 3 lesions No epithelial tumors of low malignant potential (borderline tumors) No CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases by history or evidence upon physical examination within the past 6 months Performance status - GOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 INR ≤ 1.5 PTT < 1.2 times upper limit of normal (ULN) No active bleeding or pathologic conditions carrying high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels) AST ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN Bilirubin ≤ 1.5 times ULN No acute hepatitis Creatinine ≤ 2.0 mg/dL Urine protein-creatinine ratio < 1.0 OR protein 1.0 g by 24 hour urine collection Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided the patient's cardiac status has been stable for ≥ 6 months before study entry No clinically significant cardiovascular disease, including any of the following: Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg Myocardial infarction or unstable angina within the past 6 months New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Peripheral vascular disease ≥ CTCAE grade 2 (at least brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit) No history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within the past 6 months Not pregnant or nursing Fertile patients must use effective contraception during and for ≥ 6 months after completion of bevacizumab therapy No neuropathy (sensory and motor) > grade 1 No active infection requiring antibiotics No circumstances that would preclude study participation No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies No history of allergic reaction to polysorbate 80 (e.g., etoposide, vitamin E) No other invasive malignancies within the past 5 years except non-melanoma skin cancer or localized breast cancer No serious, non-healing wound, ulcer, or bone fracture No significant traumatic injury within 28 days prior to bevacizumab therapy No prior history of abdominal fistula or gastrointestinal perforation within the past 3-6 months Granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection allowed but require weekly wound examinations No clinical symptoms or signs of gastrointestinal obstruction requiring parenteral hydration and/or nutrition At least 28 days since intra-abdominal abscess and recovered At least 3 years since prior adjuvant chemotherapy for localized breast cancer Patients must remain free of recurrent or metastatic disease At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin Patient must remain free of recurrent or metastatic disease No prior radiotherapy to any portion of the abdominal cavity or pelvis No concurrent amifostine or other protective agents No concurrent major surgical procedure or open biopsy or within 28 days prior to bevacizumab therapy No core biopsy within 7 days prior to bevacizumab therapy No prior therapy for this malignancy No prior cancer treatment that contraindicates study therapy No prior anti-VEGF drug, including bevacizumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Morgan
Organizational Affiliation
Gynecologic Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Medical Center At Irvine-Orange Campus
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Cooper Hospital University Medical Center
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Riverside Methodist Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Cancer Care Associates-Midtown
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Tulsa Cancer Institute
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74146
Country
United States
Facility Name
Gynecologic Oncology Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Women and Infants Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Pacific Gynecology Specialists
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Kawasaki Medical School
City
Okayama-Ken
State/Province
Kurashiki
ZIP/Postal Code
701-0192
Country
Japan
Facility Name
Saitama Medical University International Medical Center
City
Saitama
ZIP/Postal Code
350-1298
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

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