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Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

Primary Purpose

Glioma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

bevacizumab

carmustine

About this trial

This is an interventional treatment trial for Glioma focused on measuring adult anaplastic astrocytoma, adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma.
Disease progression (confirmed by MRI, PET or both) after radiation therapy
At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.
No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer.
Karnofsky performance score at least 70
Platelet count ≥ 130/mm3.
Absolute neutrophil count ≥ 1500/mm3
Calculated creatinine clearance greater than 45 mg/dl
AST < 2 times the upper limit of normal
Bilirubin < 1.5 times the upper limit of normal
Ability to give signed informed consent
Patients must be 18 years of age or older.

Exclusion Criteria:

Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed.
Evidence of CNS hemorrhage
Requirement for therapeutic anticoagulation
Any grade 3 or greater hemorrhage within the previous 28 days
Active inflammatory bowel disease
Inadequately controlled hypertension
Any prior history of hypertensive crisis or hypertensive encephalopathy
New York Heart Association 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
Significant vascular disease
Symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment 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 study enrollment
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
Pregnant (or lactating). Use of effective means of contraception in subjects of child-bearing potential
Prior organ transplantation
Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Known acquired immune deficiency syndrome (AIDS) or HIV positive status

Sites / Locations

University of California Davis Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab and Carmustine

Arm Description

Outcomes

Primary Outcome Measures

Progression-free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

Radiographic Response to Therapy

Response measured using MRI and PET with image fusion

Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema

Measurements made by novel brain imaging

Safety and Toxicity

Subjects will be assessed clinically for toxicity prior to, during, and after each infusion. NCI CTCAE 3.0 Common Terminology Criteria (CTC) for Adverse Events for toxicity and Adverse Event Reporting will be utilized.

Overall Survival

Full Information

NCT ID

NCT00795665

First Posted

November 20, 2008

Last Updated

May 4, 2020

Sponsor

University of California, Davis

Collaborators

National Cancer Institute (NCI), Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00795665

Brief Title

Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

Official Title

Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, Davis

Collaborators

National Cancer Institute (NCI), Genentech, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with carmustine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine works in treating patients with relapsed or progressive high-grade glioma.

Detailed Description

OBJECTIVES: Primary To determine the 6-month progression-free survival of patients with relapsed or progressive high-grade gliomas treated with bevacizumab and carmustine. Secondary To evaluate the radiographic response to this regimen as measured by MRI and PET scan with image fusion. To utilize novel brain imaging to differentiate between a radiographic response due to tumor shrinkage and a radiographic response due to decreased vasogenic edema. To evaluate the safety and toxicity of this regimen in these patients. To evaluate the overall survival of these patients. OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4 hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma

Keywords

adult anaplastic astrocytoma, adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bevacizumab and Carmustine

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

Intervention Type

Drug

Intervention Name(s)

carmustine

Other Intervention Name(s)

BCNU

Intervention Description

BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

Primary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame

Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).

Secondary Outcome Measure Information:

Title

Radiographic Response to Therapy

Description

Response measured using MRI and PET with image fusion

Time Frame

One year

Title

Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema

Description

Measurements made by novel brain imaging

Time Frame

One year

Title

Safety and Toxicity

Description

Time Frame

One year

Title

Overall Survival

Time Frame

Time from first day of treatment to time of death due to any cause (up to 7 years).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma. Disease progression (confirmed by MRI, PET or both) after radiation therapy At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy. No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer. Karnofsky performance score at least 70 Platelet count ≥ 130/mm3. Absolute neutrophil count ≥ 1500/mm3 Calculated creatinine clearance greater than 45 mg/dl AST < 2 times the upper limit of normal Bilirubin < 1.5 times the upper limit of normal Ability to give signed informed consent Patients must be 18 years of age or older. Exclusion Criteria: Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed. Evidence of CNS hemorrhage Requirement for therapeutic anticoagulation Any grade 3 or greater hemorrhage within the previous 28 days Active inflammatory bowel disease Inadequately controlled hypertension Any prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association 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 Significant vascular disease Symptomatic peripheral vascular disease Evidence of bleeding diathesis or coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment 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 study enrollment 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 Pregnant (or lactating). Use of effective means of contraception in subjects of child-bearing potential Prior organ transplantation Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Known acquired immune deficiency syndrome (AIDS) or HIV positive status

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert T. O'Donnell, MD, PhD

Organizational Affiliation

University of California, Davis

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California Davis Cancer Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

12. IPD Sharing Statement

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Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

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