Clinical trial NCT00866723: Avastin in Patients With Epithelial Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Primary Peritoneal Serous Cancer
Fallopian Tube Cancer
Keywords: Avastin
bevacizumab
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Massachusetts General Hospital
name: Genentech, Inc.
First posted: 2009-03-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Response Rate
timeFrame: 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.
measure: Clinical Benefit Response Rate
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Panagiotis Konstantinopoulos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Konstantinopoulos PA, Berlin ST, Campos SM, Matulonis UA, Cannistra SA. Bevacizumab rechallenge after first line maintenance bevacizumab. Gynecol Oncol. 2012 May;125(2):510-1. doi: 10.1016/j.ygyno.2012.02.013. Epub 2012 Feb 21. No abstract available.