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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00079430

Collaborator

Gynecologic Oncology Group (Other)

113

Enrollment

Locations

Arm

5.9

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Procedure: adjuvant therapy Drug: paclitaxel Drug: carboplatin Biological: bevacizumab	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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.
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:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

113 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2004

Actual Primary Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab) 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.	Procedure: adjuvant therapy Drug: paclitaxel Given IV Other Names: Anzatax Asotax TAX Taxol Drug: carboplatin Given intraperitoneally Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Arm

Intervention/Treatment

Experimental: Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)

Procedure: adjuvant therapy

Drug: paclitaxel

Given IV

Other Names:

Anzatax

Asotax

TAX

Taxol

Drug: carboplatin

Given intraperitoneally

Other Names:

Carboplat

CBDCA

JM-8

Paraplat

Paraplatin

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Outcome Measures

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) [3 weeks]
Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel at the MTD, assessed by CTCAE v3.0 [12 weeks]
Number of observed DLTs in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0 [6 weeks]

Secondary Outcome Measures

Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0 [12 weeks]
Response rate (in patients with measurable disease who are in the expanded cohort) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [Up to 1 year]
Progression-free survival assessed by RECIST [From study entry until disease progression, death or date of last contact, up to 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Medical Center At Irvine-Orange Campus	Orange	California	United States	92868
2	University of Chicago	Chicago	Illinois	United States	60637
3	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
4	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
5	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
6	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
7	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
8	Cancer Care Associates-Midtown	Tulsa	Oklahoma	United States	74104
9	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
10	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103
11	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
12	Women and Infants Hospital	Providence	Rhode Island	United States	02905
13	M D Anderson Cancer Center	Houston	Texas	United States	77030
14	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
15	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
16	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
17	University of Washington Medical Center	Seattle	Washington	United States	98195
18	Kawasaki Medical School	Okayama-Ken	Kurashiki	Japan	701-0192
19	Saitama Medical University International Medical Center	Saitama		Japan	350-1298