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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079430
First received: March 8, 2004
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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

Secondary Outcome Measures:
  • Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Progression-free survival assessed by RECIST [ Time Frame: From study entry until disease progression, death or date of last contact, up to 1 year ] [ Designated as safety issue: No ]

Enrollment: 113
Study Start Date: June 2004
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079430

Locations
United States, California
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
United States, Oklahoma
Cancer Care Associates-Midtown
Tulsa, Oklahoma, United States, 74104
Tulsa Cancer Institute
Tulsa, Oklahoma, United States, 74146
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Gynecologic Oncology Group
Philadelphia, Pennsylvania, United States, 19103
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Pacific Gynecology Specialists
Seattle, Washington, United States, 98104
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
Japan
Kawasaki Medical School
Okayama-Ken, Kurashiki, Japan, 701-0192
Saitama Medical University International Medical Center
Saitama, Japan, 350-1298
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Morgan Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079430     History of Changes
Other Study ID Numbers: NCI-2009-00620, NCI-2009-00620, GOG-9917, CDR0000355741, GOG-9917, GOG-9917, U10CA027469
Study First Received: March 8, 2004
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Brenner Tumor
Carcinoma
Cystadenocarcinoma
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Cystic, Mucinous, and Serous
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases

ClinicalTrials.gov processed this record on July 22, 2014