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

NCT01478321 | Terminated Phase 2 Results DMC

• 3 other identifiers: NU 11C02STU00053636NCI CTRP#
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma

Keywords

Information Not Provided

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab.

  Data will be analyzed using Kaplan-Meier curves. OS is defined as the time from first re-irradiation treatment until death from any cause.

  From treatment initiation and every 8 weeks for up to 53.5 months

Secondary Outcomes (3)

• Patient Reported Quality of Life (QOL)

  Completed before treatment (baseline) after Cycle 1 (approximately week 15) and Cycle 2 (approximately week 23)of adjuvant treatment and at the end of treatment (up to 7 cycles of adjuvant treatment, where 1 cycle =8 weeks)

• Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab

  Completed weekly during initial phase of 5 weeks and 2 weeks recovery, then every cycle during adjuvant therapy where 1 cycle =8 weeks (for up to 7 cycles)

• Percentage of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months

  At 6 and 12 months after the start of treatment

Study Arms (1)

Treatment (radiation, chemotherapy, monoclonal antibody)

EXPERIMENTAL

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; Radiation: hypofractionated radiation therapy; Biological: bevacizumab; Other: questionnaire administration

Interventions

Temozolomide DRUG

Given PO

Also known as: TMZ

Treatment (radiation, chemotherapy, monoclonal antibody)

hypofractionated radiation therapy RADIATION

Undergo hypofractionated radiation therapy

Treatment (radiation, chemotherapy, monoclonal antibody)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody,

Treatment (radiation, chemotherapy, monoclonal antibody)

questionnaire administration OTHER

Ancillary studies

Treatment (radiation, chemotherapy, monoclonal antibody)

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Edward Cancer Center

Naperville, Illinois, 60540, United States

Location

Central Dupage Hospital

Warrenville, Illinois, 60555, United States

Location

MeSH Terms

Conditions

Astrocytoma; Ependymoma; Oligodendroglioma; Glioblastoma

Interventions

Temozolomide; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was closed to accrual before the accrual goal was met due to slow accrual

Results Point of Contact

• Title: Karan Dixit, MD
• Organization: Northwestern University

karan.dixit@northwestern.edu

312-695-1301

Study Officials

• Jeffrey Raizer, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 23, 2011
• Study Start: December 14, 2011
• Primary Completion: September 12, 2018
• Study Completion: September 12, 2018
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2019-07

Locations

US (5)