A Randomized Phase 2 Trial of Cediranib and Olaparib Compared to Bevacizumab in Patients With Recurrent Glioblastoma Who Have Not Received Prior VEGF Therapy

Who is this study for? Patients with Glioblastoma
Status: Active, not recruiting
Location: See all (27) locations...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has come back (recurrent). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• Unequivocal evidence of progressive disease on contrast-enhanced brain computed tomography (CT) or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or have documented recurrent glioblastoma on diagnostic biopsy

• Previous therapy with at least radiotherapy and temozolomide

• Must be 12 weeks from radiotherapy; if patients are within 12 weeks of radiotherapy, then the progressive lesion must be outside of the high-dose radiation target volume or have unequivocal evidence of progressive tumor on a biopsy specimen

• Only first and second recurrences of GBM are eligible

• From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from investigational agents, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other systemic anti-tumor therapies; treatment on study may start one day after discontinuation of the optune device

• All adverse events grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia

• Willingness to release archival tissue sample for research purposes, if available

• Karnofsky performance status >= 60

• Life expectancy of at least 3 months

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomization

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

• Creatinine should not exceed the institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2

• Urine protein: creatinine (UPC) ratio < 1 or urine dipstick for proteinuria =< 2+ (note: if the UPC ratio is >= 1.0 then a 24-hour urine collection should be performed and this must demonstrate =< 1 g of protein in 24 hours)

• CT or MRI within 14 days prior to start of study drug

• Corticosteroid dose must be stable or decreasing for at least 5 days prior to the baseline MRI scan

• The effects of olaparib and cediranib on the developing human fetus are unknown; female subjects must either be of non-reproductive potential, not breast-feeding or must have a negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of olaparib + cediranib administration

• Ability to understand and the willingness to sign a written informed consent document

Locations
United States
California
UC San Diego Moores Cancer Center
La Jolla
Colorado
University of Colorado Hospital
Aurora
Connecticut
Smilow Cancer Hospital-Derby Care Center
Derby
Smilow Cancer Hospital Care Center-Fairfield
Fairfield
Smilow Cancer Hospital Care Center - Guiford
Guilford
Smilow Cancer Hospital Care Center at Saint Francis
Hartford
Smilow Cancer Center/Yale-New Haven Hospital
New Haven
Yale University
New Haven
Smilow Cancer Hospital-Orange Care Center
Orange
Smilow Cancer Hospital-Torrington Care Center
Torrington
Smilow Cancer Hospital Care Center-Trumbull
Trumbull
Smilow Cancer Hospital-Waterbury Care Center
Waterbury
Smilow Cancer Hospital Care Center - Waterford
Waterford
Florida
Moffitt Cancer Center
Tampa
Kentucky
University of Kentucky/Markey Cancer Center
Lexington
Massachusetts
Dana-Farber Cancer Institute
Boston
Massachusetts General Hospital Cancer Center
Boston
Missouri
Siteman Cancer Center at West County Hospital
Creve Coeur
Siteman Cancer Center at Christian Hospital
Saint Louis
Siteman Cancer Center-South County
Saint Louis
Washington University School of Medicine
Saint Louis
Siteman Cancer Center at Saint Peters Hospital
Saint Peters
North Carolina
Duke University Medical Center
Durham
New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
Ohio
Ohio State University Comprehensive Cancer Center
Columbus
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh
Time Frame
Start Date: September 15, 2017
Estimated Completion Date: December 31, 2022
Participants
Target number of participants: 70
Treatments
Experimental: Arm A (olaparib, cediranib maleate)
Patients receive olaparib PO BID and cediranib maleate PO once QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm B (bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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