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

NCT00782756 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 08-126
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Brain Cancer; Malignant Glioma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Safety assessments and toxicity grading will follow CTCAE Version 4 Grade

  through study completion, an average of 1 year

Secondary Outcomes (2)

• Progression Free Survival

  through study completion, an average of 1 year

• Neurocognitive Outcome

  through study completion, an average of 1 year

Study Arms (1)

RT, with temozolomide and bevacizumab

EXPERIMENTAL

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

Interventions

radiotherapy (RT) in combination with temozolomide and bevacizumab OTHER

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.

RT, with temozolomide and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (3)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan-Kettering Cancer Center at Commack

Commack, New York, 11725, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Glioma; Glioblastoma

Interventions

Radiotherapy; Temozolomide; Bevacizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Philip Gutin
• Organization: Memorial Sloan Kettering Cancer Center

gutinp@mskcc.org

212-639-8556

Study Officials

• Antonio Omuro, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: October 28, 2008
• Primary Completion: March 23, 2017
• Study Completion: March 23, 2017
• Last Updated: February 6, 2018
• Results First Posted: February 6, 2018

Record last verified: 2017-03

Locations

US (3)