Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma (UCDCC#208)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00795665
First received: November 20, 2008
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Glioma
Drug: bevacizumab
Drug: carmustine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from first day of treatment to the first observation of disease progression or death due to any cause. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response to therapy [ Time Frame: One year ] [ Designated as safety issue: No ]
    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 [ Time Frame: One year ] [ Designated as safety issue: No ]
    Measurements made by novel brain imaging

  • Safety and Toxicity [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Time from first day of treatment to time of death due to any cause. ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: June 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00795665

Locations
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Genentech
Investigators
Principal Investigator: Robert T. O'Donnell, MD, PhD University of California, Davis
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT00795665     History of Changes
Other Study ID Numbers: CDR0000626157, P30CA093373
Study First Received: November 20, 2008
Last Updated: July 23, 2014
Health Authority: United States: Institutional Review Board

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
Carmustine
Bevacizumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014