Cediranib Maleate and Olaparib Compared to Bevacizumab in Treating Patients With Recurrent Glioblastoma

Running, not enrolling · Phase 2

Conditions studied: Recurrent Glioblastoma

In brief

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.

Key facts

Study ID

NCT02974621

Run by

National Cancer Institute (NCI)

People needed

70

Starts

2017-12-07

Expected to finish

2026-07-17

Last updated by the study team

2026-07-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• Participants should not have received any other investigational agents nor have participated in an investigational trial within the past 4 weeks
• Participants may not have had prior use of PARP inhibitors; patients may not have received prior treatment affecting the VEGF pathway including but not limited to thalidomide, bevacizumab, sunitinib, or sorafenib
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, cediranib or bevacizumab
• Participants may not have any evidence of ongoing inadequately controlled hypertension (defined as a systolic blood pressure [BP] of > 140 mmHg or a diastolic BP of > 90 mmHg); patients with hypertension may not be on more than three antihypertensive medications for management of their blood pressure (medications that combine two anti-hypertensives into one are considered as two medications); it is strongly recommended that patients who require three antihypertensive medications for baseline management of pre-existing hypertension be actively followed by a cardiologist or blood pressure specialist for management of BP while on protocol
• Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy
• Participants may not have had history of abdominal fistula or gastrointestinal perforation within the past 6 months
• Participants may not have had a history of intra-abdominal abscess within the past 6 months
• Patients may not have a known or confirmed history of pneumonitis
• Participants may not have current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
• Participants may not have a dependency on IV hydration or total parenteral nutrition (TPN)
• Patients with myelodysplastic syndrome/acute myeloid leukemia
• Participants with any concomitant or prior invasive malignancies are ineligible with the following exceptions:
• Treated limited-stage basal cell or squamous cell carcinoma of the skin
• Carcinoma in situ of the breast or cervix
• Prior cancer treated with curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence
• Participants with any of the following:
• History of myocardial infarction within six months
• Unstable angina
• History of cerebrovascular accident (CVA) within 6 months
• New York Heart Association grade II or greater congestive heart failure
• Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
• Clinically significant peripheral vascular disease
• If cardiac function assessment is clinically indicated or performed: participants will be ineligible if left ventricular ejection fraction (LVEF) is less than normal per institutional guidelines, or < 55%, if the threshold for normal is not otherwise specified by institutional guidelines
• Participants may not have corrected QT (QTc) > 470 msec or family history of long QT syndrome

Where it is running

• UC San Diego Moores Cancer Center — La Jolla, California, United States
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Smilow Cancer Hospital-Orange Care Center — Orange, Connecticut, United States
• Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States
• Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
• Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Siteman Cancer Center-South County — St Louis, Missouri, United States
• Siteman Cancer Center at Christian Hospital — St Louis, Missouri, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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