Safety Study Of Avastin And Pelvic Radiation In Women With Recurrent Gynecological Cancers

Ovarian Cancer Clinical Trial

Official title:

A Pilot Study Evaluating The Safety Of Avastin And Pelvic Radiation In Women With Pelvic-Confined Recurrence of Gynecological Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545792
• Other study ID #: 07-042
• Secondary ID: AVF3998s
• Status: Completed
• Phase: Phase 2
• First received: October 15, 2007
• Last updated: September 10, 2015
• Start date: May 2007
• Est. completion date: October 2013

Study information

• Verified date: September 2015
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: October 2013
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma of the Vulva
• Cervical Cancer
• Endometrial Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Uterine Cervical Neoplasms
• Vaginal Cancer
• Vaginal Neoplasms
• Vulvar Neoplasms

Intervention

Drug:
• Avastin
Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (7)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Genentech, Inc., Lowell General Hospital, Massachusetts General Hospital, Saint Anne's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity Rates of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy	Toxicity was the cumulative number of events, all grades and categories, related to side effects from avastin and radiation including, but not limited to, bowel, bladder, skin, gynecologic and other morbidity.	1-year	No
Secondary	Single Point Estimate of 1-year Progression-free Survival of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy	Progression free survival was calculated from the date of diagnosis to the date of disease progression as detected by clinical examination or imaging.	1-year	No