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

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00545792
• Collaborator: Genentech, Inc. (Industry), Brigham and Women's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other), Lowell General Hospital (Other), Saint Anne's Hospital (Other)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 77
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer; Endometrial Cancer; Ovarian Cancer; Vaginal Cancer; Carcinoma of the Vulva	Drug: Avastin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Evaluating The Safety Of Avastin And Pelvic Radiation In Women With Pelvic-Confined Recurrence of Gynecological Cancers
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avastin Avastin	Drug: Avastin; Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.; Other Names: Bevacizumab

Outcome Measures

Primary Outcome Measures

1. Toxicity Rates of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy [1-year]

   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.

Secondary Outcome Measures

1. Single Point Estimate of 1-year Progression-free Survival of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy [1-year]

   Progression free survival was calculated from the date of diagnosis to the date of disease progression as detected by clinical examination or imaging.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Paul Nguyen, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul Nguyen, MD, Paul Nguyen MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00545792
• Other Study ID Numbers: 07-042; AVF3998s
• First Posted: Oct 17, 2007
• Last Update Posted: Mar 15, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Paul Nguyen, MD, Paul Nguyen MD, Dana-Farber Cancer Institute: 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
• Additional relevant MeSH terms: Ovarian Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Bevacizumab

Study Results

Participant Flow

Recruitment Details	Recruitment period was between 2008-2010. Patients seen in consultation in a gynecologic oncology or radiation oncology clinic at any of the participating institutions and recommended to undergo radiation for recurrent gynecological cancer were evaluated for eligibility.
Pre-assignment Detail	Pretreatment evaluations included medical interview, blood pressure check, complete blood count, chemistries, urine analysis and liver function tests. Tumor biopsy was performed at diagnosis. Radiologic imaging (CT, PET-CT, or MR) was performed at diagnosis.

Arm/Group Title	Avastin
Arm/Group Description	Avastin and daily radiation Avastin : Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.
Period Title: Overall Study
STARTED	21
COMPLETED	20
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Avastin
Arm/Group Description	Avastin and daily radiation Avastin : Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 61.9%
>=65 years	8 38.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (8.5)
Sex: Female, Male (Count of Participants)
Female	21 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	Toxicity Rates of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy
Description	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.
Time Frame	1-year

Outcome Measure Data

Analysis Population Description

20 patients received and completed treatment.

Arm/Group Title	Avastin
Arm/Group Description	Avastin and daily radiation Avastin : Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.
Measure Participants	20
Number [Events]	766

2. Secondary Outcome

Title	Single Point Estimate of 1-year Progression-free Survival of Patients Treated With Concurrent Avastin and Daily Pelvic Radiation With no Other Concurrent Chemotherapy
Description	Progression free survival was calculated from the date of diagnosis to the date of disease progression as detected by clinical examination or imaging.
Time Frame	1-year

Outcome Measure Data

Analysis Population Description

20 patients received and completed treatment.

Arm/Group Title	Avastin
Arm/Group Description	Avastin and daily radiation Avastin : Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.
Measure Participants	20
Number [participants]	16 76.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avastin
	Comments	Single-arm feasibility study; Kaplan Meier analysis was applied to estimate one-year PFS distribution as well as to calculate proportion of patients remain progression free by month 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Single point estiamte of 1-yr PFS
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported 1-year PFS rate 80% (Exact 95% CI: 56% - 94%) was the proportion of the patients remained progression free after 12 months.

Adverse Events

Time Frame	1 year
Arm/Group Title	Avastin
Arm/Group Description	Avastin and daily radiation Avastin : Avastin will be administered intravenously (vein) at 10mg/kg every two weeks starting day 1 for a total of 3 doses.
All Cause Mortality
	Avastin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Avastin
	Affected / at Risk (%)	# Events
Total	8/20 (40%)
Blood and lymphatic system disorders
Lymphopenia	4/20 (20%)	4
Gastrointestinal disorders
Hemorrhage, GI	1/20 (5%)	1
Vascular disorders
Thrombosis/thrombus/embolism	2/20 (10%)	2
Portal Vein Flow	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Avastin
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Hemoglobin	12/20 (60%)	35
Leukocytes	19/20 (95%)	66
Lymphopenia	17/20 (85%)	63
Neutrophils/granulocytes	5/20 (25%)	7
Platelets	14/20 (70%)	28
Cardiac disorders
Palpitation	1/20 (5%)	1
Hypertension	7/20 (35%)	14
Ear and labyrinth disorders
Tinnitus	1/20 (5%)	1
Gastrointestinal disorders
Diarrhea	18/20 (90%)	42
Nausea	10/20 (50%)	18
Other Gastrointestinal event	14/20 (70%)	60
General disorders
Fatigue	18/20 (90%)	57
Weight change	4/20 (20%)	9
Hemorrhage	9/20 (45%)	31
Edema	5/20 (25%)	11
Pain	15/20 (75%)	42
Infections and infestations
Infection	6/20 (30%)	8
Investigations
Coagulation	1/20 (5%)	2
Metabolism and nutrition disorders
Hyperglycemia	18/20 (90%)	44
Other metabolic/laboratory	19/20 (95%)	125
Musculoskeletal and connective tissue disorders
Musculoskeletal event	3/20 (15%)	7
Nervous system disorders
Neurological event	8/20 (40%)	16
Psychiatric disorders
Mood Alteration	5/20 (25%)	7
Renal and urinary disorders
Genitourinary/bladder event	11/20 (55%)	20
Reproductive system and breast disorders
Gynecologic symptoms	4/20 (20%)	5
Respiratory, thoracic and mediastinal disorders
Pulmonary event	5/20 (25%)	14
Skin and subcutaneous tissue disorders
Dermatologic symptoms	14/20 (70%)	28
Vascular disorders
Vascular event	1/20 (5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.