Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT01478321
First received: November 17, 2011
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

This phase II trial studies how well giving hypofractionated radiation therapy together with temozolomide and bevacizumab works in treating patients with high-grade glioblastoma multiforme or anaplastic glioma. Specialized radiation therapy, such as hypofractionated radiation therapy, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving hypofractionated radiation therapy together with temozolomide and bevacizumab may kill more tumor cells.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Drug: Temozolomide
Radiation: hypofractionated radiation therapy
Biological: bevacizumab
Other: questionnaire administration
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy of Hypofractionated Radiation Therapy With Bevacizumab and Temozolomide Followed by Maintenance Temozolomide and Bevacizumab for Recurrent High-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • OS [ Time Frame: Every 2 months or up to 90 days ] [ Designated as safety issue: No ]
    Data will be analyzed using Kaplan-Meier curves. Defined as the time from first re-irradiation treatment until death from any cause.


Secondary Outcome Measures:
  • Change in neurological status [ Time Frame: Baseline, weekly during radiation therapy, monthly during adjuvant phase, and then every 2 months or up to 90 days post-treatment ] [ Designated as safety issue: No ]
    Determined by examinations, patient-reported outcomes, and performance status.

  • Safety profile [ Time Frame: Baseline, weekly during radiation therapy, and prior to each course ] [ Designated as safety issue: Yes ]
    Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.

  • PFS [ Time Frame: At 3, 6, and 12 months ] [ Designated as safety issue: No ]
    Defined as the time from the first study treatment to the first occurrence of disease progression or death. Data will be analyzed using Kaplan-Meier curves.


Estimated Enrollment: 80
Study Start Date: November 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (radiation, chemotherapy, monoclonal antibody)

CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Temozolomide
Given PO
Other Name: TMZ
Radiation: hypofractionated radiation therapy
Undergo hypofractionated radiation therapy
Biological: bevacizumab
Given IV
Other Name: anti-VEGF humanized monoclonal antibody,
Other: questionnaire administration
Ancillary studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the overall survival (OS) for patients with recurrent high grade malignant gliomas treated with concurrent radiation, temozolomide, and bevacizumab followed by adjuvant temozolomide and bevacizumab.

SECONDARY OBJECTIVES:

I. Determine the impact of this regimen on neurologic symptoms via Functional Assessment of Cancer Therapy-Brain (FACT-Br) and FACT-Fatigue scales and Eastern Cooperative Oncology Group (ECOG) performance status.

II. Determine the safety profile of this regimen. III. Determine the progression free survival (PFS) at 6 and 12 months (all patients) as well as at 3 months (bevacizumab-exposed patients only).

OUTLINE:

CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on day 0. Patients also receive temozolomide orally (PO) once daily (QD) and bevacizumab intravenously (IV) over 30-90 minutes once every 2 weeks beginning on days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4

    • Patients must have measurable or non-measurable (evaluable) disease recurrence
    • Recurrence must be documented based on a combination of clinical and imaging parameters, consistent with routine clinical practice, with or without histologic confirmation
    • Patients may have had any number of relapses and be eligible for the study
    • Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naïve - Groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed -Groups 2 and 4); therapy with these agents may be given together or sequentially in the past
    • All patients may have had prior surgery, chemotherapy, and radiation therapy; prior biologic therapy is permitted only for bevacizumab-exposed patients (Groups 2 and 4); prior treatment with Gliadel is permitted for all groups
    • For bevacizumab-naïve patients (Groups 1 and 3) a minimum of 6 months must have elapsed since completion of radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy; for bevacizumab-exposed patients (Groups 2 and 4) no minimum time since completion of last radiation therapy, biologic agents, or chemotherapy will be required for study entry
    • Patients must have an ECOG performance status of =< 2
    • Hemoglobin >= 10
    • Platelets >= 100,000/mm^3
    • Absolute neutrophil count >= 1500/mm^3
    • Bilirubin =< 1.5 x upper limit of normal range (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
    • Blood urea nitrogen (BUN) =< 1.5 x ULN
    • Creatinine =< 1.5 x ULN
    • Urine protein/creatinine ratio should be =< 1
    • Patients' baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic < 140 mmHg, diastolic < 90 mmHg)
    • Patients must have a baseline evaluation including history and physical examination with neurological evaluation and magnetic resonance imaging (MRI) of the brain (with and without gadolinium-based contrast), all completed within 30 days prior to initiation of treatment
    • Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to enrollment on study; child-bearing potential is defined as any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets one of the following criteria:

      • Has not undergone a hysterectomy or bilateral oophorectomy
      • Or has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding consecutive 12 months)
    • Females of child-bearing potential and sexually-active males must consent to follow acceptable birth control methods to avoid contraception while on treatment
    • All subjects must have given signed, informed consent prior to registration on study
    • Patients previously treated outside of Northwestern must have their pathology slides sent to Northwestern for review and confirmation - NOTE: a copy of the pathology report is sufficient for registration

Exclusion Criteria:

  • • Patients who are pregnant or breast-feeding will NOT be eligible for participation

    • Patients with a prior malignancy will NOT be eligible for participation aside from the following exception:

  • Patients who have had any curatively treated malignancy and have been disease free without treatment for 1 year prior to study entry ARE eligible for participation

    • Patients with an active second malignancy (other than non-melanoma skin cancer or cervical cancer in situ) are NOT eligible for participation
    • Patients with uncontrolled hypertension (>= 140/90 mmHg) are NOT eligible for participation
    • Patients who exhibit any other serious concurrent infection or other medical illness which would jeopardize their ability to receive the therapy outlined in this protocol with reasonable safety will NOT be eligible for participation
    • The eligibility criteria listed above are interpreted literally and cannot be waived
  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: NCT01478321

Contacts
Contact: Study Coordinator 3126951301 cancertrials@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Jeffrey Raizer, MD         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: M. K. Nicholas, MD         
Principal Investigator: M. K. Nicholas, MD         
Northwestern Lake Forest Hospital Recruiting
Lake Forest, Illinois, United States, 60045
Contact: Joseph Imperato, MD         
Principal Investigator: Joseph Imperato, MD         
Edward Cancer Center Recruiting
Naperville, Illinois, United States, 60540
Contact: William Broderick, MD         
Principal Investigator: William Broderick, MD         
Central Dupage Hospital Recruiting
Warrenville, Illinois, United States, 60555
Contact: Vinai Gondi, MD         
Principal Investigator: Vinai Gondi, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Jeffrey Raizer, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT01478321     History of Changes
Other Study ID Numbers: NU 11C02, STU00053636, NCI CTRP#
Study First Received: November 17, 2011
Last Updated: September 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Information Not Provided

Additional relevant MeSH terms:
Astrocytoma
Ependymoma
Glioblastoma
Oligodendroglioma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Antibodies, Monoclonal
Bevacizumab
Dacarbazine
Temozolomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014