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Advanced Bladder CarcinomaPhase 2NCT03375307

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 2 study testing Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy in people with Advanced Bladder Carcinoma and Advanced Genitourinary System Carcinoma, run by National Cancer Institute (NCI) at 17 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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
17 sitesUnited States
Study dates
3 Nov 2020to 16 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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
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  • 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)
  • Creatinine clearance >= 50 mL/min/1.73 m^2
  • Hemoglobin >= 9 g/dL; transfusions are allowed
  • Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on direct oral anticoagulant (DOA)
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib
  • Pre-clinical data indicate that olaparib adversely affects embryofetal survival and development. Therefore, women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least six (6) months after the last dose of olaparib. Male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib.
  • Note: Olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib
  • Ability to understand and the willingness to sign a written informed consent document or patients with impaired decision making capacity (IDMC) if they are represented by a legally authorized representative (LAR)
  • Patients must provide archival tumor sample for mutation analysis or be willing to undergo mandatory screening biopsy. In the event that the patient cannot undergo biopsy and tumor is not available, Foundation Medicine liquid biopsy will be performed
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment at screening. Note: This will also need to be confirmed within 3 days prior to treatment on day 1. Postmenopausal is defined as at least one (1) of the following:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations

Who cannot join

  • 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
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  • 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)
  • Uncontrolled diabetes mellitus
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study
  • Immunocompromised patients, e.g., those with known HIV not on highly active antiretroviral therapy (HAART) with detectable levels of virus
  • Patients with known active hepatitis (i.e., hepatitis B or C)
  • Other malignancy within the last two (2) 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 or localized resected prostate cancer may be eligible, provided they completed their adjuvant chemotherapy more than two (2) years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • NCI - Center for Cancer Research

    Bethesda, Maryland, 20892

  • UC San Diego Health System - Encinitas

    Encinitas, California, 92024

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0565

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

Other trials in United States

About this study

Official title: A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma and Other Genitourinary Tumors With DNA-Repair Defects

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the efficacy of olaparib in two cohorts of patients with metastatic/advanced non prostate genitourinary (GU) cancer pre-selected by DNA-repair defects as measured by overall response rate (ORR).

SECONDARY OBJECTIVES:

  1. To describe the effect of therapy on progression free survival (PFS). II. To describe the effect of therapy on overall survival (OS). III. To describe the safety/tolerability and drug-related toxicities of olaparib.

IV. To follow patients without the pre-selected DNA-repair defects for survival. (Cohort 3 only)

CORRELATIVE OBJECTIVES:

  1. To determine the proportion of patients with DNA-repair pathway-mutated genes in metastatic non-prostate GU cancer (patient cohort referred for screening).

II. To correlate levels of baseline circulating tumor cells (CTCs) with survival in untreated patients.

III. To explore tumor-mutational profiles in metastatic tumor biopsies, saliva "normal" DNA, changes in tumor or peripheral immune characteristics, or tumor associated somatic mutation load in blood DNA in response to treatment.

IV. To explore changes in plasma cytokines and correlate with clinical response.

  1. To correlate levels of circulating endothelial cells with clinical outcome. VI. To correlate levels of circulating tumor cells (CTCs) with clinical outcome.

VII. To correlate peripheral immune and DNA damage response transcriptional signatures with clinical outcomes.

VIII. To determine the effectiveness of using next-generation sequencing (NGS) to identify DNA-repair pathway gene defects in tumor samples and circulating DNA and identify patients with non-prostate GU cancer suitable for PARP inhibition.

IX. To determine the expression of Schlafen 11 (SLFN11) in tumor versus (vs.) stroma cells, and the potential tumor heterogeneity based on SLFN11 expression.

  1. To determine if the levels of hyaluron (HA) detected in circulating plasma correlates with outcomes in patients treated with olaparib.

XI. To determine if the levels of HGF and MET detected in circulating plasma correlates with outcomes in patients with olaparib.

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT I and II: Patients that have cancer-associated DNA-repair gene mutations receive olaparib orally (PO) twice daily (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, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, or bone scan and optional tumor biopsy and bone marrow biopsy on study.

COHORT III: Patients 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.

After completion of study treatment, patients are followed up at 4 weeks, every 2 months for 1 year, then every 3 months thereafter.

Being tested
Biopsy Procedure, Biospecimen Collection, Bone Marrow Biopsy, Bone Scan, Computed Tomography
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

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

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tumor biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood collection

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • OlaparibDrug

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

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT03375307
Study groupRoleWhat they receive
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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Olaparib; Procedure: Positron Emission Tomography
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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

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

  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.

    Measured: Up to 5 years

Secondary outcomes (4)

  1. Overall survival (OS)

    OS will be calculated using the Kaplan-Meier method, starting at the date that the participant was first considered to be included in that set of participants undergoing treatment or observation.

    Measured: Up to 5 years

  2. Progression free survival (PFS)

    PFS will be determined using a Kaplan-Meier curve, with probabilities at various time points indicated along with appropriate confidence intervals.

    Measured: 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

  3. Incidence of adverse events

    Will be assessed according to the Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 5 years

  4. Individual deoxyribonucleic acid (DNA)-repair defects

    The association between individual DNA-repair defects and ORR will be determined using Fisher's exact test.

    Measured: Up to 5 years

Timeline

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

  1. First posted18 Dec 2017
  2. Study start3 Nov 2020
  3. Primary completion16 Dec 2026 (estimated)
  4. Study completion16 Dec 2026 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03375307
Sponsor's protocol ID
NCI-2017-02296
Other IDs
NCI-2017-02296, P162941, 19C0023, 10144, 10144, ZIABC011078
Status last verified
Jun 2026
First submitted
15 Dec 2017
Last updated
11 Jun 2026
Results posted
No
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 Biopsy Procedure, Biospecimen Collection and Bone Marrow Biopsy in people with Advanced Bladder Carcinoma and Advanced Genitourinary System Carcinoma, run by National Cancer Institute (NCI) at 17 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 30 inclusion and 24 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 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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?

This study is still under way. Results are not available in the source record yet.

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?

Overall response rate (ORR) (time frame: Up to 5 years). 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 NCT03375307.

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 11 Jun 2026.

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