Avastin +/- Erlotinib Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Primary Peritoneal Cancer; Clear Cell Mullerian Tumor; Fallopian Tube Cancer; Ovarian Cancer; Papillary Serous Mullerian Tumor

Treatments: Drug: bevacizumab; Drug: carboplatin; Drug: erlotinib; Drug: paclitaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00520013

07-039

Details and patient eligibility

About

The purpose of this research study is to evaluate how patients with newly diagnosed advanced ovarian, fallopian tube, primary peritoneal cancer and papillary serous or clear cell mullerian tumors respond to consolidation therapy with Avastin and erlotinib or Avastin alone over 1 year. These drugs have been used in the treatment of other types of cancers and information from those studies suggests that these agents may help to treat the cancers studied here.

Full description

Objectives:

Primary To examine the progression free survival (PFS) of Avastin and Erlotinib (AE) or Avastin (A) as consolidation therapy.

Secondary To examine the toxicity between the two consolidative regimens AE vs. A. To assess the response rate of CTA.

STATISTICAL DESIGN This study uses a randomized selection design. Both consolidation treatment arms are deemed experimental and are compared against a historical control [McGuire WP et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. NEJM 1996: 334:1-6. PMID:7494563]. With 30 patients in a given arm and 6 months of follow-up, there was 80% power to detect a 61.5% increase in median PFS from 13 months to 21 months assuming 1-sided 10% significance.

Enrollment: 60 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age and older
• Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, primary peritoneal carcinoma, or papillary serous mullerian carcinoma
• Previous attempted surgical debulking
• Stage III or IV
• Willing and able to undergo second look laparoscopy
• Performance status 0-1 by ECOG scale
• Peripheral neuropathy < grade 2
• Life expectancy of 6 months or greater

Exclusion criteria

• Patients with clinically significant cardiovascular disease as outlined in the protocol
• Neutrophil count < 1,500/mm3; platelet count <100,000/m3
• Alkaline phosphatase or bilirubin > 1.5 x ULN, SGOT > 5 x ULN
• Calculated creatinine clearance < 50ml/min
• Prior chemotherapy or radiotherapy for other malignancy except for the treatment for localized breast cancer greater than five years prior to diagnosis
• No more than one cycle of first line chemotherapy with carboplatin and paclitaxel
• Inadequate surgical cytoreduction such that interval cytoreductive surgery could materially improve prognosis
• Concurrent invasive malignancy
• Evidence of bleeding diathesis or coagulopathy
• Evidence of tumor involving major blood vessels on any prior CT scans
• Surgical wound that has failed to close
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of this study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0
• Serious non-healing wound, ulcer, or bone fracture
• Prior treatment with an anti-angiogenic agent
• Any active bleeding
• Active psychiatric disease or neurologic symptoms requiring treatment
• Presence of central nervous system brain metastases
• Proteinuria at screening as demonstrated by criteria in protocol
• Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent
• Known hypersensitivity to Cremophor EL or any component of Avastin
• Active bacterial, viral, or fungal infections
• Receiving any other investigational agent
• History of gastrointestinal perforation
• Prior therapies targeting the epidermal growth factor receptor
• Symptoms of bowel obstruction
• Dependence on TPN or IV hydration

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

carboplatin/paclitaxel/bevacizumab then bevacizumab

Experimental group

Description:

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.

Treatment:

Drug: paclitaxel

Drug: carboplatin

Drug: bevacizumab

carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib

Experimental group

Description:

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.

Treatment:

Drug: paclitaxel

Drug: erlotinib

Drug: carboplatin

Drug: bevacizumab

carboplatin/paclitaxel/bevacizumab

Experimental group

Description:

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None

Treatment:

Drug: paclitaxel

Drug: carboplatin

Drug: bevacizumab