Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma

• ClinicalTrials.gov Identifier: NCT00782756
• Recruitment Status: Completed
• First Posted: October 31, 2008
• Results First Posted: February 6, 2018
• Last Update Posted: February 6, 2018
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.; National Institutes of Health (NIH)
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Brain Cancer; Malignant Glioma	Other: radiotherapy (RT) in combination with temozolomide and bevacizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma
• Actual Study Start Date: October 28, 2008
• Actual Primary Completion Date: March 23, 2017
• Actual Study Completion Date: March 23, 2017

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: through study completion, an average of 1 year ]
   Safety assessments and toxicity grading will follow CTCAE Version 4 Grade

Secondary Outcome Measures :

1. Progression Free Survival [ Time Frame: through study completion, an average of 1 year ]
2. Neurocognitive Outcome [ Time Frame: through study completion, an average of 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

  Study Documents (Full-Text)

Documents provided by Memorial Sloan Kettering Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] April 28, 2009

More Information

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00782756
• Other Study ID Numbers: 08-126
• First Posted: October 31, 2008
• Results First Posted: February 6, 2018
• Last Update Posted: February 6, 2018
• Last Verified: March 2017

• Studies a U.S. FDA-regulated Drug Product: Yes

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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action