Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Information provided by (Responsible Party):
Susana M. Campos, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00520013
First received: August 22, 2007
Last updated: June 13, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Papillary Serous Mullerian Tumor
Clear Cell Mullerian Tumor
Drug: bevacizumab
Drug: erlotinib
Drug: paclitaxel
Drug: carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Consolidation Progression-Free Survival [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Consolidation Treatment-related Toxicity Rate [ Time Frame: Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year. ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Consolidation Objective Response Rate [ Time Frame: Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year. ] [ Designated as safety issue: No ]
    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.


Enrollment: 60
Study Start Date: August 2007
Study Completion Date: November 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: bevacizumab
Other Names:
  • Avastin
  • rhuMAB VEGF
Drug: paclitaxel
Other Name: Taxol
Drug: carboplatin
Other Name: Paraplatin
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: bevacizumab
Other Names:
  • Avastin
  • rhuMAB VEGF
Drug: erlotinib
Other Name: Tarceeva
Drug: paclitaxel
Other Name: Taxol
Drug: carboplatin
Other Name: Paraplatin
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: bevacizumab
Other Names:
  • Avastin
  • rhuMAB VEGF
Drug: paclitaxel
Other Name: Taxol
Drug: carboplatin
Other Name: Paraplatin

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00520013

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Genentech, Inc.
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Investigators
Principal Investigator: Susana Campos, MD, MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Susana M. Campos, MD, Medical Oncologist., Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00520013     History of Changes
Other Study ID Numbers: 07-039 
Study First Received: August 22, 2007
Results First Received: April 8, 2015
Last Updated: June 13, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Mixed Tumor, Mullerian
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Bevacizumab
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Erlotinib Hydrochloride
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on September 30, 2016