Clinical trial NCT00545792: Safety Study Of Avastin And Pelvic Radiation In Women With Recurrent Gynecological Cancers
Official title: A Pilot Study Evaluating The Safety Of Avastin And Pelvic Radiation In Women With Pelvic-Confined Recurrence of Gynecological Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Endometrial Cancer
Ovarian Cancer
Vaginal Cancer
Carcinoma of the Vulva
Keywords: Recurrent Endometrial cancer
Recurrent Cervical cancer
Recurrent Ovarian cancer
Recurrent Vaginal cancer
Recurrent Vulvar cancer
Vaginal recurrence
Brachytherapy
Radiation Treatment
External Beam Radiation
Avastin
Bevacizumab
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Brigham and Women's Hospital
name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: Lowell General Hospital
name: Saint Anne's Hospital
First posted: 2007-10-17
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is evaluating a drug called avastin in combination with standard radiation as a possible treatment for treatment for recurrent pelvic-confined gynecological cancer (i.e. endometrial, cervical, vulvar, ovarian or vaginal cancers).

Detailed description: The purpose of this research study is to learn the effects (good and bad) of an antiangiogenic therapy drug (drugs that stop new blood vessel growth and starve a tumor by cutting off its blood supply) called avastin. Avastin is an antibody directed against vascular endothelial growth factor, or VEGF. VEGF is a potent, specific growth factor with a well-defined role in normal and abnormal blood vessel formation. It is present in a wide variety of normal tissues, but is produced in excess by most solid cancers (tumors). In the setting of cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. In laboratory studies, avastin has been shown to inhibit the growth of several different types of human cancer cells.

This drug has been studied in at least 3500 people with breast, colorectal, renal, ovarian and lung cancer. It has not been studied in combination radiation therapy in people with recurrent gynecological cancer.

Previous clinical trials involving the use of avastin in combination with standard radiation in colorectal and pancreatic cancer show no significant increase in toxicity as compared to standard radiation therapy toxicity.

The primary objective of this study is to assess the toxicity of administering avastin with radiation for recurrent gynecological cancer. The secondary endpoint will be to assess the time to progression of the disease. This means we hope this treatment program will delay any regrowth of your cancer as compared to standard therapy with radiotherapy alone. In addition, how well you respond to the treatment, patterns of remission or recurrence will be measured.

Eligibility criteria: Inclusion Criteria:

* All patients (age \> 18 years) will have locally recurrent gynecological cancer with a component of disease that will fit within a standard RT portal at the time of presentation
* ECOG performance status score 0-1
* All patients will have had a prior hysterectomy
* Histological confirmation of recurrent gynecological cancer, including adenocarcinoma, papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma
* Age \> 18 years
* Radiologic work-up computer tomography of the chest and abdomen, and computer tomography or MR of the pelvis confirming pelvis-confined recurrence
* Adequate renal function as evidenced by serum creatinine \< 1.5 mg/dL
* Adequate hepatic function as evidenced by:

Serum total bilirubin \< 1.5 mg/dL SGOT/SGPT \< 3X the ULN for the reference lab

* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients with a prior history of full course external beam radiation therapy to the pelvis (patients with prior vaginal brachytherapy may be included)
* Inability to comply with study and/or follow-up procedures
* Life expectancy of less than 12 weeks
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored avastin cancer study
* Known CNS disease (including history of encephalitis, multiple sclerosis or seizure disorder), except for treated brain metastasis
* Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to study enrollment
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Known CNS disease (including history of encephalitis, multiple sclerosis or seizure disorder)
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Any surgical procedure requiring an incision, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for any surgical procedure requiring an incision during the course of the study (excluding vascular access device placement or procedures that do not require an incision)
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Serious, non-healing wound, ulcer, or bone fracture
* Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of avastin
* Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to give informed consent or cooperate and participate in the study or to interfere with the investigator's ability to interpret the results

Primary outcomes:
measure: Toxicity Rates of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy
timeFrame: 1-year
Secondary outcomes:
measure: Single Point Estimate of 1-year Progression-free Survival of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy
timeFrame: 1-year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Paul Nguyen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Viswanathan AN, Lee H, Berkowitz R, Berlin S, Campos S, Feltmate C, Horowitz N, Muto M, Sadow CA, Matulonis U. A prospective feasibility study of radiation and concurrent bevacizumab for recurrent endometrial cancer. Gynecol Oncol. 2014 Jan;132(1):55-60. doi: 10.1016/j.ygyno.2013.10.031. Epub 2013 Nov 4.