Clinical trial NCT00520013: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Papillary Serous Mullerian Tumor
Clear Cell Mullerian Tumor
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Beth Israel Deaconess Medical Center
name: Brigham and Women's Hospital
name: Massachusetts General Hospital
First posted: 2007-08-23
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Consolidation Progression-Free Survival
timeFrame: 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.
measure: Consolidation Treatment-related Toxicity Rate
timeFrame: 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 outcomes:
measure: Consolidation Objective Response Rate
timeFrame: Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Susana Campos, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: