Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma - Full Text View

Purpose

The purpose of this study is to test the safety of a new plan for treating glioblastoma. The usual first treatment for glioblastoma is to give focused radiation over 6 weeks in combination with a chemotherapy called temozolomide. In this study the radiation will be given over 2 weeks in combination with temozolomide and another drug, bevacizumab, will also be given. Our idea is that this treatment plan may attack both the tumor and the blood vessels feeding the tumor more effectively. This study will look at what effects, good or bad, this approach has on the patient and the tumor.

Condition	Intervention	Phase
Brain Cancer Malignant Glioma	Other: radiotherapy (RT) in combination with temozolomide and bevacizumab	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

Resource links provided by NLM:

Drug Information available for: Temozolomide Bevacizumab

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:

To test the safety and efficacy of bevacizumab and temozolomide in combination with hypo-fractionated radiotherapy inpatients with newly diagnosed glioblastoma in terms of improvements in overall survival. [ Time Frame: conclusion of the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression free survival [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
Neurocognitive outcome [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]


Enrollment:	40
Study Start Date:	October 2008
Estimated Study Completion Date:	October 2017
Estimated Primary Completion Date:	October 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: RT, with temozolomide and bevacizumab This treatment regimen is novel in that it delivers the initial course of RT over 2 weeks instead of 6 weeks; also, the addition of bevacizumab during and after RT is a new approach.	Other: radiotherapy (RT) in combination with temozolomide and bevacizumab Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions. Post RT therapy: Bevacizumab 10mg/kg IV every two weeks. Temozolomide 150-200mg/m2 daily for 5 consecutive days will be given on 28 day cycles. Follow up: CBC weekly, comprehensive panel and urinalysis monthly, blood pressure every other week. Neurological/physical examination monthly. Gd-enhanced MRI with perfusion every 2 cycles. Neurocognitive testing (approximately 4months post RT, 1 year after diagnosis and then annually in long term survivors). Blood sample for correlative studies monthly.

Arms

Assigned Interventions

Experimental: RT, with temozolomide and bevacizumab

This treatment regimen is novel in that it delivers the initial course of RT over 2 weeks instead of 6 weeks; also, the addition of bevacizumab during and after RT is a new approach.

Other: radiotherapy (RT) in combination with temozolomide and bevacizumab

Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions.

Post RT therapy: Bevacizumab 10mg/kg IV every two weeks. Temozolomide 150-200mg/m2 daily for 5 consecutive days will be given on 28 day cycles.

Follow up: CBC weekly, comprehensive panel and urinalysis monthly, blood pressure every other week. Neurological/physical examination monthly. Gd-enhanced MRI with perfusion every 2 cycles. Neurocognitive testing (approximately 4months post RT, 1 year after diagnosis and then annually in long term survivors). Blood sample for correlative studies monthly.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pathologic diagnosis of glioblastoma or grade IV glioma.
Tumor volume should be less than 60 cc (approximately 5cm maximum diameter).
Age > or = to 18
KPS ≥70
Granulocyte count >1.5 X 10 9/L
Platelet count >99 X 10 9/L
SGOT < 2.5X upper limit of normal (ULN)
Serum creatinine < 2X ULN
Bilirubin < 2X ULN
All patients must sign written informed consent

Exclusion Criteria:

Any prior chemotherapy, radiotherapy and biologic therapy for glioma.
Any prior experimental therapy for glioma.
Multicentric glioma
Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin).
Serious medical or psychiatric illness that would in the opinion of the investigator interfere with the prescribed treatment.
Pregnant or breast feeding women.
Refusal to use effective contraception
Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
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 12 months prior to Day 1
History of stroke or transient ischemic attack
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment 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 access device, within 7 days prior to Day 1
History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
Serious, non-healing wound, active ulcer, or untreated bone fracture
Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening
Known hypersensitivity to any component of bevacizumab

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00782756

Locations


United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Genentech, Inc.

National Institutes of Health (NIH)

Investigators


Principal Investigator:	Antonio Omuro, MD	Memorial Sloan Kettering Cancer Center

More Information


Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00782756 History of Changes
Other Study ID Numbers:	08-126
Study First Received:	October 29, 2008
Last Updated:	July 25, 2016
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center:


Radiation BEVACIZUMAB AVASTIN TEMOZOLOMIDE newly diagnosed	Glioblastoma GBM malignant glioma Radiotherapy 08-126

Additional relevant MeSH terms:


Glioma Brain Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases	Nervous System Diseases Bevacizumab Temozolomide Dacarbazine Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016