Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes
A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma and Other Genitourinary Tumors With DNA-Repair Defects
5 other identifiers
interventional
60
1 country
17
Brief Summary
This phase II trial studies how well olaparib works in treating patients with bladder cancer and other genitourinary tumors with deoxyribonucleic acid (DNA)-repair defects that has spread to other places in the body (advanced or metastatic) and usually cannot be cured or controlled with treatment. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing.
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 Nov 2020
Longer than P75 for phase_2
17 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
December 15, 2017
CompletedFirst Posted
Study publicly available on registry
December 18, 2017
CompletedStudy Start
First participant enrolled
November 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 16, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 16, 2026
June 11, 2026
June 1, 2026
6.1 years
December 15, 2017
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall response rate (ORR)
Will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). ORR will be reported along with 95% exact confidence intervals.
Up to 5 years
Secondary Outcomes (4)
Overall survival (OS)
Up to 5 years
Progression free survival (PFS)
From the date of olaparib initiation to investigator-assessed clinical progression or radiographic progression (by RECIST), or death from any cause, whichever occurs first, assessed up to 5 years
Incidence of adverse events
Up to 5 years
Individual deoxyribonucleic acid (DNA)-repair defects
Up to 5 years
Study Arms (2)
Cohort I (olaparib)
EXPERIMENTALPatients that have cancer-associated DNA-repair gene mutations receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, MRI, PET/CT, or bone scan and optional tumor biopsy and bone marrow biopsy on study.
Cohort II (biospecimen collection)
EXPERIMENTALPatients that do not have cancer-associated DNA-repair gene mutations undergo blood sample collection at baseline. Additionally, patients undergo CT, MRI, PET/CT, or bone scan and optional tumor biopsy and bone marrow biopsy on study.
Interventions
Undergo PET/CT
Undergo tumor biopsy
Given PO
Undergo bone scan
Undergo CT or PET/CT
Undergo MRI
Undergo blood collection
Undergo bone marrow biopsy
Eligibility Criteria
You may qualify if:
- Patients must have a histologically confirmed diagnosis non-prostate GU cancer
- Patients with the presence of cancer-associated genetic mutations in one or more pathogenic or likely pathogenic gene alterations tested in the FoundationOne FoundationOne®CDx (F1CDx) panel will be enrolled in cohorts 1 or 2 as follows:
- Cohort 1: BRCA1, BRCA2, ATM, BAP1, PALB2, and BRIP1, or tumor mutational burden (TMB) where 10 or greater mutations/megabase
- ABL1, FANCE, POLD1, ATR, FANCG, POLE, ATRX, FANCL, RAD51, BARD1, IKBKE, SMARCB1, BRD4, MEN1, STK11, CCND1, MLH1, TP53, CHEK1, MSH2, CHEK2, MSH6, DOT1L, MUTYH, FANCA, NPM1, FANCC, PMS2
- Patients with benign or variants of unknown significance as determined by FoundationOne FoundationOne®CDx (F1CDx) panel and Genetics Review Panel review will be enrolled in Cohort 3 to be followed for survival
- Foundation One mutation analysis results performed prior to enrollment on this study may be accepted for eligibility review and in the event that a patient cannot undergo a biopsy and tumor is not available, Foundation Medicine liquid biopsy may be performed
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam
- Evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) during treatment or after the most recent dose of therapy with at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor (atezolizumab, pembrolizumab, nivolumab, avelumab or durvalumab) (2-week washout from chemotherapy and 4-weeks washout from monoclonal antibodies is required)
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of olaparib in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (or Karnofsky \>= 70%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) (for subjects with documented Gilbert's disease total bilirubin =\< 3.0 mg/dL)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (for subjects with liver metastasis AST/ALT =\< 5 x ULN)
- +15 more criteria
You may not qualify if:
- Patients who have had prior treatment with olaparib or any other PARP inhibitor (PARPi)
- Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated
- Persistent toxicities (\>= Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2) with the exception of alopecia or peripheral neuropathy, caused by previous cancer therapy
- Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility
- Patients with known 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. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
- History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib
- Patients receiving strong or moderate CYP3A inhibitors or inducers are ineligible. A washout period prior to the first dose of olaparib for patients on CYP3A inhibitors/inducers is 5 half-lives or 3 weeks , whichever is shorter. Medications with limited systemic absorption (e.g., ophthalmic, otic) do not require a washout and are permitted.
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference texts such as the Physicians' Desk Reference. 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
- Pregnant women are excluded from this study because olaparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects
- Any chronic or concurrent acute liver disease
- History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to enrollment
- Uncontrolled concurrent disease or illness including but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
- Unstable or untreated cardiac conditions or ejection fraction of \< 50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
UC San Diego Health System - Encinitas
Encinitas, California, 92024, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, 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
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
NCI - Center for Cancer Research
Bethesda, Maryland, 20892, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Texas Medical Branch
Galveston, Texas, 77555-0565, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrea B Apolo
National Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 15, 2017
First Posted
December 18, 2017
Study Start
November 3, 2020
Primary Completion (Estimated)
December 16, 2026
Study Completion (Estimated)
December 16, 2026
Last Updated
June 11, 2026
Record last verified: 2026-06