Bevacizumab Study With Carboplatin & Paclitaxel in Ovarian, Fallopian Tube or Primary Peritoneal Cancer

This study has been terminated.
(Did not meet accrual goals.)
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by:
University of Connecticut Health Center
ClinicalTrials.gov Identifier:
NCT00408070
First received: December 5, 2006
Last updated: November 16, 2010
Last verified: November 2010
  Purpose

The primary objective is to determine whether the addition of bevacizumab to a regimen of carboplatin plus paclitaxel significantly improves Progression Free Survival (PFS) for patient with Stage III suboptimally cytoreduced or Stage IV ovarian, primary peritoneal or fallopian tube carcinomas.


Condition Intervention Phase
Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Stage 3 Cancer
Stage 4 Cancer
Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Connecticut Health Center:

Primary Outcome Measures:
  • Progression Free Survival Rate at 9 Months [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    This Outcome is measuring the number of particpants who have survived.


Secondary Outcome Measures:
  • Response to Treatment (Clinical/Pathological) [ Time Frame: not assessed; study terminated early ] [ Designated as safety issue: No ]
  • Rate of Decline of CA-125 [ Time Frame: not assessed; study terminated early ] [ Designated as safety issue: No ]
  • To Determine the Degree and Type of Toxicity of This Combined Regimen [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Determine Tolerability to 12 Months (q 3 Weeks) of Bevacizumab Maintenance Therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: October 2006
Study Completion Date: October 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
This is a single Arm study. Two of the study drugs used are non-experimental. One of the study drugs is experimental.
Drug: Bevacizumab
cycle 2 (6 cycles re-evaluated and follow up)
Other Name: Avastin (brand name)
Drug: Carboplatin
cycle #1 and continuous through entire regimen; treated every 3 weeks
Other Name: Paraplatin
Drug: Paclitaxel
cycle #1 and continuous through entire regimen; treated every 3 weeks
Other Name: Taxol (brand name)

  Hide Detailed Description

Detailed Description:

The aim of this study is to determine if the addition of bevacizumab to a regimen of carboplatin/paclitaxel increases the time to disease recurrence (longer remission for patients) in women that have Stage III suboptimally reduced or Stage IV ovarian cancer.

The hypothesis is that the addition of bevacizumab to a carboplatin/paclitaxel regimen will increase progression free survival in subjects that have Stage III suboptimal cytoreduced or Stage IV ovarian cancer.

Scientific Background and Significance: Vascular endothelial growth factor (VEGF) is found in most tissues, and is known to regulate angiogenesis in both normal (e.g. ovulation) and abnormal (e.g. malignant tumors) conditions. VEGF has been found to be overexpressed in several tumor types, including breast, bladder, uterine, cervical, and relevant to this application, primary and metastatic tumors of patients with advanced ovarian cancer. It is widely believed that the overexpression of this factor contributes to tumorigenesis by supplying a conduit through which oxygen and nutrients can reach and feed the growing malignancy.

Treatment with an anti-VEGF antibody may help to exert a direct anti-angiogenic effect by binding to and clearing VEGF from the tumor microenvironment, thus preventing the formation of new blood vessels. Bevacizumab is a recombinant humanized anti-VEGF monoclonal antibody that inhibits the growth of a number of human cancers, including ovarian cancer. Additional antitumor activity may be obtained through the effects of bevacizumab on tumor vasculature, interstitial pressure, and blood vessel permeability, all of which could allow for enhanced delivery of concurrently administered chemotherapeutic agents to tumor cells.

Based on preliminary data (Proc Am Soc Clin Oncol 2005; 23:A5000 and A 5009), there is biologic rationale to use bevacizumab in the treatment of advanced ovarian cancer. These 2 preliminary studies reported an improved progression-free survival in patients with recurrent ovarian cancer with the use of bevacizumab in combination with chemotherapy. Based on this activity in the recurrent setting, the activity of bevacizumab needs to be evaluated in chemotherapy-naïve patients with advanced ovarian cancer. The purpose of this clinical trial is to determine whether the addition of bevacizumab to a regimen of carboplatin and paclitaxel significantly improves Progression Free Survival (PFS) in patients with Stage III suboptimally cytoreduced or Stage IV ovarian, primary peritoneal or fallopian tube carcinomas.

It is apparent that newer innovative therapies are needed in the front line setting to decrease recurrences and improve survival. The addition of bevacizumab, the anti-vascular endothelial growth factor antibody, to the standard carboplatin/taxol treatment paradigm might help to increase the long-term survival rates in patients newly diagnosed with advanced suboptimal ovarian cancer. The proposed study addresses this issue. The investigational plan that will be utilized to test the hypothesis that the addition of bevacizumab extends the survival time of the affected patients is outlined below.

Women with Stage III or IV ovarian cancer/primary peritoneal cancer/fallopian tube cancer that have undergone surgery with residual suboptimally cytoreduced disease (suboptimal defined as >1cm disease) will be eligible for treatment with one 21-day cycle of carboplatin and paclitaxel and five 21-day cycles of bevacizumab, carboplatin and paclitaxel for a total of six treatment cycles; bevacizumab treatment is delayed by one cycle to ensure adequate post-surgical healing. Subjects will be evaluated by CT scans to determine response to therapy; individuals that progress will be withdrawn from the study. The CT scan conducted after the completion of therapy will dictate the next course of action. Patients demonstrating a complete response will be maintained on bevacizumab as consolidation therapy; subjects demonstrating a partial response will continue to receive bevacizumab, carboplatin and paclitaxel. The total treatment time for patients with a clinical response following the initial 6 cycles of therapy will be 12 months. Prior to starting consolidation therapy, all patients with a complete clinical response or in those for whom surgery may result in a complete secondary cytoreduction, will be given the option of undergoing a second look surgery. The findings at surgery in combination with the CT scan will determine the response to initial therapy. The decision not to participate in the second look surgery will not affect the follow-up treatment that the patient will receive.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of primary peritoneal carcinoma, fallopian tube epithelial ovarian carcinoma,
  • stage III suboptimal surgery or biopsy,
  • stage IV disease
  • no prior chemotherapy

Exclusion Criteria:

  • unstable heart conditions
  • high blood pressure
  • vascular disorders
  • bleeding problems
  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: NCT00408070

Locations
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
Sponsors and Collaborators
University of Connecticut Health Center
Genentech, Inc.
Investigators
Principal Investigator: Carolyn Runowicz, MD University of Connecticut Health Center
  More Information

Additional Information:
No publications provided

Responsible Party: Carolyn Runowicz, MD, Univ. of CT Health Center
ClinicalTrials.gov Identifier: NCT00408070     History of Changes
Other Study ID Numbers: AVF 3696s, IRB 06-337-1
Study First Received: December 5, 2006
Results First Received: October 14, 2010
Last Updated: November 16, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Connecticut Health Center:
ovarian cancer
fallopian tube cancer
peritoneal cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Bevacizumab
Carboplatin
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 22, 2014