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

A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Papillary Serous Mullerian Tumor; Clear Cell Mullerian Tumor
• Intervention / Treatment: Drug: carboplatin; Drug: paclitaxel; Drug: bevacizumab; Drug: erlotinib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carboplatin/paclitaxel/bevacizumab then bevacizumab; 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.	Drug: carboplatin; Other Names: Paraplatin; Drug: paclitaxel; Other Names: Taxol; Drug: bevacizumab; Other Names: Avastin; rhuMAB VEGF
Experimental: carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib; 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.	Drug: carboplatin; Other Names: Paraplatin; Drug: paclitaxel; Other Names: Taxol; Drug: bevacizumab; Other Names: Avastin; rhuMAB VEGF; Drug: erlotinib; Other Names: Tarceeva
Experimental: carboplatin/paclitaxel/bevacizumab; 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	Drug: carboplatin; Other Names: Paraplatin; Drug: paclitaxel; Other Names: Taxol; Drug: bevacizumab; Other Names: Avastin; rhuMAB VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consolidation Progression-Free Survival	Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.	Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.
Consolidation Treatment-related Toxicity Rate	Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.	Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consolidation Objective Response Rate	Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample.	Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Massachusetts General Hospital; Beth Israel Deaconess Medical Center; Genentech, Inc.; Brigham and Women's Hospital
• Investigators: Principal Investigator: Susana Campos, MD, MPH, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 22, 2007
• First Submitted That Met QC Criteria: August 22, 2007
• First Posted (Estimate): August 23, 2007

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Peritoneal Diseases; Genital Neoplasms, Female; Adnexal Diseases; Digestive System Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Neoplasms, Complex and Mixed; Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Mixed Tumor, Mullerian; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Erlotinib Hydrochloride; Bevacizumab
• Other Study ID Numbers: 07-039