Hypofractionated Stereotactic Radiotherapy With Bevacizumab in the Treatment of Recurrent Malignant Glioma

NCT01392209 | Completed Phase 1

• 1 other identifier: 11-057
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief Summary

The best dose of radiation to be given with bevacizumab is currently unknown. This study will use higher doses of radiation with bevacizumab than have been used before. This study will test the safety of radiation given at different doses with bevacizumab to find out what effects, good and/or bad, it has on the patient and the malignant glioma or related brain cancers.

Conditions

Brain Cancer; MALIGNANT GLIOMA; Glioblastoma; Anaplastic Astrocytoma (AA); Anaplastic Oligodendroglioma (AO); Anaplastic Oligo-astrocytoma (AOA); Anaplastic Mixed Gliomas; Malignant Glioma NOS

Keywords

BEVACIZUMAB; HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY; Brain; CNS; anti-VEGF antibody; 11-057

Outcome Measures

Primary Outcomes (1)

• To establish the maximum tolerated dose (MTD)

  of hypofractionated stereotactic re-irradiation delivered with concomitant bevacizumab in recurrent malignant gliomas (using a standard 3+3 design).

  1 year

Secondary Outcomes (6)

• Response rate

  1 year

• Median progression free survival

  1 year

• 6 month progression-free survival rate

  1 year

• Median overall survival

  1 year

• Use of tractography to predict routes of progression in gliomas (MSKCC only)

  1 year

Study Arms (1)

Bevacizumab & Stereotactic Radiotherapy

EXPERIMENTAL

This will be a multicenter (MSKCC and UCSF) phase I dose escalation study to determine the maximum tolerated dose (MTD) of hypofractionated stereotactic radiotherapy when administered in combination with a fixed dose of bevacizumab.

Other: Bevacizumab & Stereotactic Radiotherapy

Interventions

Bevacizumab & Stereotactic Radiotherapy OTHER

Treatment: (until treatment failure): bevacizumab 10 mg/kg IV once every two weeks on days 1 (+/- 3 days) and 15 (+/- 3 days) of every cycle (Cycle defined as 28 days). On day 28 (or up to 2 days before) of cycles 1 and 2 (and for every other cycle thereafter) patients will undergo a physical and radiological re-evaluation (MRI). Patients will begin stereotactic radiotherapy beginning anywhere from day 7 to day 10 of cycle 2 with escalating fraction sizes (interpatient - there is no intrapatient escalation). Assessment of response will be performed following cycles 1 and 2 then following every two cycles.

Bevacizumab & Stereotactic Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Patients must have EITHER
• Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma, Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligo-astrocytoma (AOA) also called anaplastic mixed gliomas, Malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made.
• Participating site confirmation is adequate.
• Able to undergo brain MRI scans.
• MRI scan with gadolinium contrast showing geographically-circumscribed tumor ≤40 cc incorporating both enhancing and non-enhancing volume. This is calculated by the product of maximum measurements in 3 dimensions divided by 2. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. (The MRI must be performed on a steroid dosage that has been stable or decreasing for at least 5 days. Patients on no steroids are eligible. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required).
• Prior treatment with approximately 60 Gy of radiotherapy.
• Patients must have recovered from the toxic effects of prior therapy including but not limited to:
• An interval of ≥ 4 weeks (28 days) from prior cytotoxic therapy except 6 weeks from nitrosoureas
• An interval of ≥ 1 week (7 days) from any non-cytotoxic agents
• An interval of ≥ 3 months from the completion of radiation therapy
• Absolute neutrophil count ≥ 1,500/mm3.
• Platelet count ≥ 100,000/mm3.
• Hemoglobin ≥ 10 g/dl.
• Serum creatinine ≤ 2 times upper limit of normal.
• Total bilirubin ≤ 2 times upper limit of normal.

You may not qualify if:

• Prior treatment with radiosurgery
• Prior disease progression/recurrence during or immediately following treatment with bevacizumab. Any question should be directed to the PI.
• Multicentric glioma
• Other malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) for which there has been treatment within the last 3 years
• Serious medical or psychiatric illness that would in the opinion of the investigator interferes with the prescribed treatment.
• Pregnant or breast feeding women
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Grade 2 or greater congestive heart failure
• History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to Day 1
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator
• Columbia University: collaborator
• University of California, San Francisco: collaborator

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):797-804. doi: 10.1016/j.ijrobp.2017.06.2466. Epub 2017 Jun 30.

  PMID: 28870792 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Glioma; Glioblastoma; Astrocytoma; Oligodendroglioma

Interventions

Bevacizumab; Radiosurgery

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Thomas Kaley, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2011
• First Posted: July 12, 2011
• Study Start: July 8, 2011
• Primary Completion: November 15, 2019
• Study Completion: November 15, 2019
• Last Updated: November 22, 2019

Record last verified: 2019-11

Locations

US (5)