Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate 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

Basic Trial Information

Objectives

Primary

1. 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.
2. Determine the feasibility of this regimen in these patients.
3. Determine the feasibility of adding IV bevacizumab to this regimen in courses 2-6.

Secondary

1. Determine the toxicity profile of this regimen in these patients.
2. Determine the toxicity profile of paclitaxel and bevacizumab IV in combination with intraperitoneal carboplatin in these patients.
3. 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.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

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.

Outcomes

Maximum tolerated dose of intraperitoneal (IP) carboplatin when administered with paclitaxel in course 1
Feasibility of paclitaxel and IP carboplatin treatment
Feasibility of adding IV bevacizumab to treatment

Toxicity profile of paclitaxel and IP carboplatin
Toxicity profile of IV bevacizumab added to this regimen
Response rate (in patients with measurable disease who are in the expanded cohort) and progression-free survival

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.

Morgan MA, Sill MW, Fujiwara K, et al.: A phase I study with an expanded cohort to assess the feasibility of intraperitoneal carboplatin and intravenous paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 121 (2): 264-8, 2011.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Mark Morgan, MD, FACOG, FACS, Protocol chair		Ph: 215-214-1430; 888-369-2427 Email: mark.morgan@fccc.edu

Registry Information
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
Trial Start Date		2004-06-03
Trial Completion Date		2011-05-05
Registered in ClinicalTrials.gov		NCT00079430
Date Submitted to PDQ		2004-02-05
Information Last Verified		2010-11-08
NCI Grant/Contract Number		CA27469

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