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

• ClinicalTrials.gov Identifier: NCT00795665
• Recruitment Status: Completed
• First Posted: November 21, 2008
• Results First Posted: May 12, 2020
• Last Update Posted: May 12, 2020
• Sponsor: University of California, Davis
• Collaborators: National Cancer Institute (NCI); Genentech, Inc.
• Information provided by (Responsible Party): University of California, Davis

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.

Condition or disease	Intervention/treatment	Phase
Glioma	Drug: bevacizumab; Drug: carmustine	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas
• Study Start Date: June 2008
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm

Intervention/treatment

Experimental: Bevacizumab and Carmustine

Drug: bevacizumab; 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.; Other Name: Avastin; Drug: carmustine; 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.; Other Name: BCNU

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival [ 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). ]
   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 :

1. Radiographic Response to Therapy [ Time Frame: One year ]
   Response measured using MRI and PET with image fusion
2. Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema [ Time Frame: One year ]
   Measurements made by novel brain imaging
3. Safety and Toxicity [ Time Frame: One year ]
   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.
4. Overall Survival [ Time Frame: Time from first day of treatment to time of death due to any cause (up to 7 years). ]

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:

• 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

Contacts and Locations

Locations

United States, California

University of California Davis Cancer Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

National Cancer Institute (NCI)

Genentech, Inc.

Investigators

• Principal Investigator: Robert T. O'Donnell, MD, PhD; University of California, Davis

More Information

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00795665
• Other Study ID Numbers: 224865; UCDCC#208 ( Other Identifier: UC Davis ); P30CA093373 ( U.S. NIH Grant/Contract )
• First Posted: November 21, 2008
• Results First Posted: May 12, 2020
• Last Update Posted: May 12, 2020
• Last Verified: May 2020

Keywords provided by University of California, Davis:

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

Additional relevant MeSH terms:

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Bevacizumab; Carmustine; 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