Avastin in Patients With Epithelial Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer

May 17, 2018 updated by: Panagiotis Konstantinopoulos, MD, PhD, Beth Israel Deaconess Medical Center

Phase II Study of Single-Agent Avastin in Patients With Epithelial Ovarian, Primary Peritoneal Serous, Papillary Serous Endometrial or Fallopian Tube Cancer Who Have Recurred After Prior Therapy With Maintenance Avastin

The purpose of this study is to evaluate how the participant's disease (ovarian, primary peritoneal serous, fallopian tube, or papillary serous endometrial cancer) responds to additional treatment with Avastin (bevacizumab). Participants have already received Avastin as part of maintenance therapy for their cancer. Maintenance therapy is a medical therapy that is given to people to prevent a relapse. However, cancer may return after maintenance therapy. This research study hopes to determine whether additional treatment with Avastin will be effective in treating the participant's cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary:

To determine the activity of bevacizumab in patients with epithelial ovarian, primary peritoneal serous, papillary serous endometrial or fallopian tube cancer who relapse after achieving an initial complete response to first-line therapy that included at least 6 month bevacizumab maintenance as defined by: 1) clinical response rate OR 2) clinical benefit response

Secondary:

  • To assess duration of progression free survival (PFS)
  • To assess the safety
  • To correlate response with the Avastin-free interval

STATISTICAL DESIGN:

This study used a two-stage design to evaluate efficacy of bevacizumab based on a patient achieving either clinical response or clinical benefit response. The null and alternative response rates were 10% and 30%. If two or more patients enrolled in the stage one cohort (n=10 patients) achieved response than accrual would proceed to stage two (n=19 patients). If response was achieved by at least 6 patients in the final set of 29 evaluable patients then bevacizumab would be deemed worthy for further study. This design had 80% power given one-sided 0.05 significance level.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, papillary serous endometrial cancer, or fallopian tube cancer
  • Must have responded and remained clinically stable (as defined by normal clinical examination, normal serum CA125 level and normal CT scan) after first-line platinum-based regimen followed by bevacizumab maintenance therapy
  • Must have developed relapsed disease at least 3 months after completion of bevacizumab maintenance therapy as defined by a) development of new, measurable lesions by RECIST criteria, but no lesion with maximum diameter greater than 3 centimeters OR b) newly elevated CA125 level at least 2 x ULN on 2 separate occasions, obtained at least 1 day but not more than 3 months apart
  • ECOG Performance Status 0-2
  • No prior cytotoxic chemotherapy or biologic therapy for disease recurrence allowed
  • Prior hormonal-based therapy for ovarian, primary peritoneal serous or fallopian tube cancer is allowed
  • Toxic side effects related to prior chemotherapy or hormonal therapy must have resolved to grade one or less or to baseline before initiation of bevacizumab
  • 18 years of age or older
  • Life expectancy of 6 months or greater
  • Normal organ and marrow function as outlined in the protocol

Exclusion Criteria:

  • Prior cytotoxic chemotherapy or biologic therapy for disease recurrence
  • Known CNS disease, except for treated brain metastasis
  • Pregnancy or breast feeding
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • 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 the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular device, within 7 days prior to enrollment
  • History of abdominal fistula, GI perforation, intra-abdominal abscess, or CT evidence of bowel obstruction or bowel wall thickening
  • Symptoms of intestinal obstruction, or requirement of parenteral hydration and/or nutrition
  • History of active malignancy during the last 3 years, except non-melanomatous skin cancer or in situ breast or cervical cancer
  • Evidence of preexisting uncontrolled hypertension. If patient has hypertension, it must be medically controlled (< 150/90) prior to starting bevacizumab
  • Proteinuria at screening
  • Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent
  • Therapeutic anticoagulation is not by itself and exclusion criterion. However, for certain high risk patients on therapeutic anticoagulation, eligibility will be determined after discussion with the overall PI
  • Any active bleeding
  • Serious, non-healing wound, ulcer, or bone fracture
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • NYHA Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to Day 1
  • History of stroke or transient ischemic attack within 6 months prior to day 1
  • Significant vascular disease within 6 months prior to day 1
  • History of hemoptysis within 1 month prior to day 1
  • Presence of measurable lesion(s) by RECIST criteria with maximum diameter greater than 3 centimeters

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: bevacizumab
Bevacizumab was administered at 15 mg/kg intravenously every 3 weeks. Treatment continued until disease progression or unacceptable toxicity.
Drug: bevacizumab
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response Rate
Time Frame: Disease was evaluated at baseline and every 3 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Patients underwent radiologic assessment (CT or MRI scans) and CA-125 levels were measured.
For measurable disease (MD) patients, clinical response on treatment was based on RECIST 1.0 criteria with overall response 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. 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. For non-MD patients, clinical response based on modified Gynecologic Cancer Intergroup (GCIG) criteria was defined as at least a 50% decrease in CA-125 levels.
Disease was evaluated at baseline and every 3 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Patients underwent radiologic assessment (CT or MRI scans) and CA-125 levels were measured.
Clinical Benefit Response Rate
Time Frame: Disease was evaluated at baseline and every 3 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Patients underwent radiologic assessment (CT or MRI scans) and CA-125 levels were measured.
Clinical benefit response was defined as absence of disease progression at 18 weeks (ie after 6 cycles). Disease progression (PD) could occur per RECIST 1.0 or based on CA-125 levels. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Disease progression based on CA-125 level was doubling of the CA-125 level from baseline. For patients with normal baseline CA-125 (who by definition had MD) the criterion for progression based on CA-125 doubling was doubling of CA-125 from the upper limit of normal (i.e. more than 70).
Disease was evaluated at baseline and every 3 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Patients underwent radiologic assessment (CT or MRI scans) and CA-125 levels were measured.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Massachusetts General Hospital
Dana-Farber Cancer Institute
Genentech, Inc.

Investigators

  • Principal Investigator: Panagiotis Konstantinopoulos, MD, PhD, Beth Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

March 19, 2009

First Submitted That Met QC Criteria

March 19, 2009

First Posted (Estimate)

March 20, 2009

Study Record Updates

Last Update Posted (Actual)

May 22, 2018

Last Update Submitted That Met QC Criteria

May 17, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-323

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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