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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
This study has been completed.

First Received on March 8, 2004.   Last Updated on August 11, 2011   History of Changes
Sponsor: Gynecologic Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079430
  Purpose

RATIONALE: 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.

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.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Biological: bevacizumab
Drug: carboplatin
Drug: paclitaxel
Procedure: adjuvant therapy
Phase I

Study Type: Interventional
Study Design: 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,IND #7921) 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 of intraperitoneal (IP) carboplatin when administered with paclitaxel in course 1 [ Designated as safety issue: Yes ]
  • Feasibility of paclitaxel and IP carboplatin treatment [ Designated as safety issue: No ]
  • Feasibility of adding IV bevacizumab to treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity profile of paclitaxel and IP carboplatin [ Designated as safety issue: Yes ]
  • Toxicity profile of IV bevacizumab added to this regimen [ Designated as safety issue: Yes ]
  • Response rate (in patients with measurable disease who are in the expanded cohort) and progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: June 2004
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.
  • Determine the feasibility of adding IV bevacizumab to this regimen in courses 2-6.

Secondary

  • Determine the toxicity profile of this regimen in these patients.
  • 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.

PROJECTED ACCRUAL: A total of 3-64 patients (3-24 for dose escalation and 20-40 for feasibility) will be accrued for this study within 15 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • GOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • 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)

Hepatic

  • AST ≤ 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • No acute hepatitis

Renal

  • Creatinine ≤ 2.0 mg/dL
  • Urine protein-creatinine ratio < 1.0 OR protein 1.0 g by 24 hour urine collection

Cardiovascular

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • At least 3 years since prior adjuvant chemotherapy for localized breast cancer

    • Patients must remain free of recurrent or metastatic disease

Endocrine therapy

  • Not specified

Radiotherapy

  • 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

Surgery

  • See Disease Characteristics
  • 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

Other

  • No prior therapy for this malignancy
  • No prior cancer treatment that contraindicates study therapy
  • No prior anti-VEGF drug, including bevacizumab
  • No concurrent amifostine or other protective agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079430

Locations
United States, California
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Washington
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
Japan
Saitama Medical University International Medical Center
Saitama, Japan, 350-1298
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Study Chair: Mark A. Morgan, MD, FACOG, FACS Fox Chase Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00079430     History of Changes
Other Study ID Numbers: CDR0000355741, GOG-9917
Study First Received: March 8, 2004
Last Updated: August 11, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage III ovarian epithelial cancer
stage II ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
ovarian undifferentiated adenocarcinoma
Brenner tumor
ovarian clear cell cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian mucinous cystadenocarcinoma
ovarian serous cystadenocarcinoma
primary peritoneal cavity cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Adjuvants, Immunologic
Bevacizumab
Carboplatin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on February 12, 2012