Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations
A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors
4 other identifiers
interventional
89
1 country
51
Brief Summary
This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2019
Longer than P75 for phase_2
51 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 7, 2017
CompletedFirst Posted
Study publicly available on registry
July 11, 2017
CompletedStudy Start
First participant enrolled
January 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 2, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 28, 2026
ExpectedFebruary 19, 2026
January 1, 2026
6.2 years
July 7, 2017
February 18, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall response rate
Will be determined by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 for extracranial solid tumors, Response Assessment in Neuro-Oncology criteria for intracranial glioma. Overall response rate and a 90% creditable interval in each cohort will be estimated using the approach described by Koyama. For the other solid tumors cohort, descriptive statistics and graphical displays will be used to summarize results within tumor types.
Up to completion of 8 weeks of treatment
Secondary Outcomes (2)
Progression-free survival
From start of treatment to time of progression or death, whichever occurs first, assessed up to 3.6 years
Incidence of adverse events
Up to 3.6 years
Other Outcomes (3)
2HG plasma magnetic resonance spectroscopy levels
Baseline up to post-treatment
2HG plasma concentration level
Up to 3.6 years
Co-occurring alterations
Baseline up to 3.6 years
Study Arms (1)
Treatment (olaparib)
EXPERIMENTALPatients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity, withdrawal of consent or death. Patients undergo a CT scan and/or MRI, as well as a tumor biopsy and blood sample collection on study.
Interventions
Undergo tissue biopsy
Undergo blood sample collection
Undergo a CT scan
Undergo a MRI
Given PO
Eligibility Criteria
You may qualify if:
- Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed
- Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K
- Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies
- Patients must be willing to undergo extra blood sampling for correlative studies
- Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria
- The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment
- There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI)
- For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease \< 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
- New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line)
- If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. i.e., \> 70% tumor cell nuclei in areas), high or progressive increase in MIB-1 proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor);
- Note: Given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy
- For patients with WHO grade III or IV glioma and progressive disease \>= 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
- New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids
- Increase by \>= 25% in the sum of the products of perpendicular diameters between the first post-radiotherapy scan, or a subsequent scan with smaller tumor size, and the scan at 12 weeks or later on stable or increasing doses of corticosteroids
- For patients receiving antiangiogenic therapy, significant increase in T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also be considered progressive disease; the increased T2/FLAIR must have occurred with the patient on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy and not be a result of comorbid events (e.g., effects of radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects)
- +26 more criteria
You may not qualify if:
- Involvement in the planning and/or conduct of the study
- Previous enrollment in the present study
- Participation in another clinical study with an investigational product during the last 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment (6 weeks for nitrosoureas or mitomycin C)
- Any previous treatment with PARP inhibitor, including olaparib
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for \>= 5 years; patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- Resting electrocardiogram (ECG) with corrected QT interval (QTc) \> 470 msec or family history of long QT syndrome
- Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting olaparib is 2 weeks; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; 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
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; 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
- Persistent toxicities caused by previous cancer therapy; toxicities should have recovered to =\< grade 1, excluding alopecia and stable chronic grade 2 toxicity that is not overlapping with presumed toxicities of olaparib
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
- Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days; patients with known uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Major surgery within 2 weeks of starting study treatment; effects from surgeries should have recovered to =\< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, 92627, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patricia M LoRusso
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 7, 2017
First Posted
July 11, 2017
Study Start
January 30, 2019
Primary Completion
April 2, 2025
Study Completion (Estimated)
July 28, 2026
Last Updated
February 19, 2026
Record last verified: 2026-01