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Recurrent GlioblastomaPhase 2NCT02974621

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

A Phase 2 study testing Bevacizumab, Cediranib and Cediranib Maleate in people with Recurrent Glioblastoma, run by National Cancer Institute (NCI) at 27 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Glioblastoma
What is being tested?
Bevacizumab, Cediranib and Cediranib Maleate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
27 sitesUnited States
Study dates
7 Dec 2017to 17 Jul 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Participants may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib; anticipation of need for major surgical procedures during the course of the study also excludes patients from the trial
  • Participants should not have any uncontrolled intercurrent illness including, but limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or moderate inhibitors of CYP3A4 are ineligible; the study team should check a frequently-updated medical reference for a list of drugs to avoid or minimize use of; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; dihydropyridine calcium-channel blockers are permitted for management of hypertension; patient drug information handout and wallet card should be provided to patients
  • Pregnant women are excluded from this study because cediranib and olaparib agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cediranib and olaparib breastfeeding should be discontinued if the mother is treated with cediranib and olaparib; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cediranib and olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
  • Other anti-cancer therapy while on study treatment
  • Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
  • Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown; the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, cannabis, S. John's wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto or ginseng)
  • Raloxifene is allowed for patients taking it for bone health
  • Participants should not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

United States27 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the antitumor activity of cediranib maleate (cediranib)/olaparib versus reference bevacizumab monotherapy, as measured by progression-free survival at 6 months (PF6), in patients with recurrent glioblastoma (GBM).

SECONDARY OBJECTIVES:

  1. To compare overall survival (OS), progression free survival (PFS) and objective response (ORR) in patients with recurrent GBM treated with cediranib/olaparib versus bevacizumab.

II. To assess the safety of the combination of olaparib and cediranib in patients with recurrent GBM.

III. To evaluate the association of blood based biomarkers involved with angiogenesis using the Biomarker Review Committee-approved Plasma Angiome Panel (bFGF, Ang-1, Ang-2, Tie-2, SDF1-alpha, Collagen IV, PlGF, sVEGFR1, sVEGFR2, VEGF, Il-1beta, Il-6, Il-8, TNF-alpha, CAIX) with the clinical activity of cediranib/olaparib.

IV. To evaluate the association of tissue biomarkers involved with deoxyribonucleic acid (DNA) repair using the Biomarker Review Committee-approved BROCA panel with the clinical activity of cediranib/olaparib.

  1. To identify genomic alteration by whole exome sequencing in GBM tumor specimens that correlate with the clinical activity of cediranib/olaparib.

VI. To evaluate the association of magnetic resonance imaging (MRI) imaging parameters (tumor perfusion and oxygenation, brain tumor cellularity) with the biological response of cediranib/olaparib.

VII. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

VIII. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive olaparib orally (PO) twice daily (BID) and cediranib maleate PO once daily (QD) on days 1-28.

ARM B: Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks.

In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then periodically for 3 years.

Being tested
Bevacizumab, Cediranib, Cediranib Maleate, Olaparib
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called ABP 215, ABP-215, ABP215, Alymsys

    Given IV

  • CediranibDrug

    Also called AZ-D2171, AZD 2171, AZD2171

    Given PO

  • Cediranib MaleateDrug

    Also called AZD2171, AZD2171 Maleate, Recentin

    Given PO

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU 0059436

    Given PO

Study groups in NCT02974621
Study groupRoleWhat they receive
Arm A (olaparib, cediranib maleate)ExperimentalPatients 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.
Receives: Drug: Cediranib; Drug: Cediranib Maleate; Drug: Olaparib
Arm B (bevacizumab)ExperimentalPatients receive bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Progression-Free Survival at 6 Months

    Progression-Free Survival (PFS) is defined as the time from randomization to progressive disease (PD) per Response Assessment in Neuro-Oncology (RANO) criteria, or death due to any cause, whichever occurs first. Participants alive without PD are censored at date of last disease evaluation.

    PD criteria:

    (A) 25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response or baseline if no decrease) on stable or increasing doses of steroids and/or one or more of the following: (B) Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of steroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events (C) Any new lesions (D) Clear clinical deterioration not attributable to other causes apart from the tumor, per discretion of the treating physician (E) Failure to return for evaluation due to death or deteriorating condition.

    Measured: 6 months

Secondary outcomes (7)

  1. Progression Free Survival

    Progression free survival is defined as the time from randomization until progressive disease or death from any cause.

    Measured: Up to 3 years

  2. Overall Survival (OS)

    Overall Survival (OS) is defined as the time from randomization to death due to any cause, or censored at date last known alive.

    Measured: up to 3 years

  3. Incidence of Adverse Events (AE)

    The grade of adverse events be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. The incidence of an adverse event at a particular grade is the number of patients who experienced that adverse event/grade.

    Measured: Up to 3 years

  4. Levels of Circulating Cytokines Involved With Angiogenesis

    Descriptive statistics will be provided for all continuous biomarkers outcomes. Contingency tables will be provided for categorical data. All comparisons between study arms will be adjusted for multiplicity and in particular false discovery rate (FDR) (Hochberg and Binaymini) will be used for genome data. Binary endpoints will be reported using 95% binomial confidence intervals.

    Measured: Up to 3 years

  5. Levels of Serial Circulating Biomarkers Involved With Deoxyribonucleic Acid (DNA) Repair

    Descriptive statistics will be provided for all continuous biomarkers outcomes. Contingency tables will be provided for categorical data. All comparisons between study arms will be adjusted for multiplicity and in particular FDR (Hochberg and Binaymini) will be used for genome data. Binary endpoints will be reported using 95% binomial confidence intervals.

    Measured: Up to 3 years

  6. Tumor Genomic Alteration

    Will be assessed by whole exome sequencing. Descriptive statistics will be provided for all continuous biomarkers outcomes. Contingency tables will be provided for categorical data. All comparisons between study arms will be adjusted for multiplicity and in particular FDR (Hochberg and Binaymini) will be used for genome data. Binary endpoints will be reported using 95% binomial confidence intervals.

    Measured: Up to 3 years

  7. Imaging Correlates (Vascular Permeability, Tumor Perfusion and Oxygenation, Brain Tumor Cellularity)

    Descriptive statistics will be provided for all continuous biomarkers outcomes. Contingency tables will be provided for categorical data. All comparisons between study arms will be adjusted for multiplicity and in particular FDR (Hochberg and Binaymini) will be used for genome data. Binary endpoints will be reported using 95% binomial confidence intervals.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2016 (estimated)
  2. Study start7 Dec 2017
  3. Primary completion31 Dec 2022
  4. Study completion17 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02974621
Sponsor's protocol ID
NCI-2016-01769
Other IDs
NCI-2016-01769, 17-735, 10067, 10067, UM1CA186709
Status last verified
Jul 2026
First submitted
23 Nov 2016
Last updated
15 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Cediranib and Cediranib Maleate in people with Recurrent Glioblastoma, run by National Cancer Institute (NCI) at 27 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Progression-Free Survival at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02974621.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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