Metastatic Urothelial CancerPhase 2NCT03448718

Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations

A Phase 2 study testing Olaparib in people with Metastatic Urothelial Cancer, run by Matthew Galsky at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a single arm open label multi-institutional phase II trial of olaparib monotherapy in subjects with metastatic urothelial cancer harboring somatic DNA damage response (DDR) alterations. The primary objective of the study is to estimate the objective response rate (per RECIST 1.1) to treatment with olaparib. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Urothelial Cancer
What is being tested?: Olaparib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 7 sitesUnited States
Study dates: 17 Apr 2018to 15 Oct 2021
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

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of ≤ 1 within 14 days prior to registration. Cisplatin-ineligible chemotherapy-naïve subjects (see inclusion criteria #8) may have an ECOG Performance Status of ≤ 2.
Histological or cytological evidence/confirmation of urothelial cancer.
Metastatic and/or unresectable (cT4b) urothelial cancer.
Metastatic disease evaluable on imaging studies. Subjects may have measurable disease according to RECIST 1.1 or bone-only disease within 30 days prior to registration.

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NOTE: Bone-only subjects are eligible if their disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria.34
NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.
Somatic alteration considered pathogenic/likely pathogenic in one of the following DDR genes as determined by genomic sequencing performed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory. Somatic alterations will include nonsense, frameshift, splice-site or missense mutations or homozygous deletions. Subjects with alterations in DDR genes not included in the list below will be considered on a case by case basis after discussion with the sponsor-investigator(s). Subjects with germline alterations in DDR genes will be considered on a case by case basis and will be reviewed by the sponsor-investigator(s). At least 6 subjects will have BRCA or ATM alterations.
Nucleotide Excision Repair: ERCC2, ERCC3,ERCC4, ERCC5, ERCC6
Homologous Recombination: BRCA1, RAD52, BRCA2, RAD54L, RAD50, NBN RAD51, MRE11A, RAD51B, RAD51D, RAD51C, CTIP
DNA Sensor: ATM, ATR, MDC1, ATRX, CHEK1, CHEK2
Fanconi Anemia Pathway: PALB2, FANCE, BRIP1, FANCF, FANCA, FANCG FANCB, BLM, FANCC, FANCD2
Base Excision Repair: XRCC2, XRCC3, XRCC4, XRCC5, XRCC6
Other: MUTYH, RECQL4, POLQ, POLE, WRN
A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic
Subjects must have progressed despite at least 1 prior line of treatment for metastatic and/or unresectable urothelial cancer. However, cisplatin-ineligible (defined by a calculated creatinine clearance of >30 but < 60 mL/min OR CTCAE v4 Grade ≥ 2 audiometric hearing loss OR CTCAE v4 Grade ≥ 2 peripheral neuropathy OR ECOG PS = 2), and chemotherapy-naïve subjects are also eligible.
Prior cancer treatment (systemic therapy or radiation therapy) must be completed at least 3 weeks prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
Hemoglobin (Hgb) ≥ 9 g/dL
Platelets ≥ 100 x 109/L
Calculated creatinine clearance ≥ 30 mL/min
Bilirubin ≤ 1.5 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
Alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
Female subjects must be postmenopausal or there must be evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 90 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Males must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 90 days after treatment discontinuation.
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
15. All subjects must have adequate archival tissue available prior to registration (i.e., at least 15 unstained slides or paraffin block). Archival tissue should represent invasive or metastatic urothelial cancer with a preference for metastatic tissue if available. Archival tissue should be identified at screening and shipped by C1D1. Subjects without adequate tissue may be considered on a case by case basis after discussion with the sponsor-investigator.

Who cannot join

Active infection requiring systemic therapy.
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Known additional malignancy that is active and/or progressive requiring treatment; subjects with other malignancies that have been definitively treated and who have been rendered disease free will be eligible.
Prior treatment with a PARP inhibitor, including olaparib.
Treatment with any investigational drug within 30 days prior to registration.
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

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Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery.
Subjects 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, history of pneumonitis, or any psychiatric disorder that prohibits obtaining informed consent.
Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.
Subjects with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
University of Chicago Medical Center
Chicago, Illinois, 60637
Karmanos Cancer Center (Wyane State University)
Detroit, Michigan, 48201
Vanderbilt-Ingran Cancer Center
Nashville, Tennessee, 37232
Icahn School of Medicine at Mount Sinai
New York, New York, 10029-6542
Huntsman Cancer Institute University of Utah
Salt Lake City, Utah, 84112-5550

Other trials in United States

About this study

Official title: Phase 2 Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations

Conditions: Metastatic Urothelial Cancer
Being tested: Olaparib

What participants receive

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

OlaparibDrug
Also called Lynparza
1 cycle = 28 days. Subject's with calculated creatinine clearance (CrCl) of ≥ 40 mL/min will start at a dose of olaparib tablets of 300 mg twice a day. Subjects with a CrCl of > 30 to < 40 mL/min will start at a dose of olaparib tablets 200 mg twice a day.

Study groups in NCT03448718
Study group	Role	What they receive
Olaparib Monotherapy	Experimental	The starting dose of olaparib tablets will be dependent on the subject's calculated creatinine clearance (CrCl). Subjects with a CrCl of ≥ 40 mL/min will start at a dose of olaparib tablets of 300 mg twice a day. Subjects with a CrCl of > 30 to < 40 mL/min will start at a dose of olaparib tablets 200 mg twice a day. Receives: Drug: Olaparib

What is being measured

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

Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.
ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.
Measured: Up to a maximum of 17 months

Secondary outcomes (1)

Progression-Free Survival (PFS)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
Measured: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 17 months.

Timeline

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

17 Apr 201815 Oct 2021

First posted28 Feb 2018
Study start17 Apr 2018
Primary completion14 Jul 2021
Study completion15 Oct 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Metastatic Urothelial CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03448718
Sponsor's protocol ID: HCRN GU15-262
Status last verified: Nov 2023
First submitted: 22 Feb 2018
Last updated: 22 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
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RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 3
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma

All Metastatic Urothelial Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2 Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations
ClinicalTrials.gov ID: NCT03448718
Acronym / sponsor ID: HCRN GU15-262
Conditions: Metastatic Urothelial Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Matthew GalskyUniversity, hospital or other
Collaborators: Icahn School of Medicine at Mount Sinai, AstraZeneca
Study start: 17 Apr 2018 (actual)
Primary completion: 14 Jul 2021 (actual)
Study completion: 15 Oct 2021 (actual)
First posted: 28 Feb 2018 (actual)
Results: Posted 22 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Olaparib Monotherapy	Experimental	Drug: OlaparibThe starting dose of olaparib tablets will be dependent on the subject's calculated creatinine clearance (CrCl). Subjects with a CrCl of ≥ 40 mL/min will start at a dose of olaparib tablets of 300 mg twice a day. Subjects with a CrCl of > 30 to < 40 mL/min will start at a dose of olaparib tablets 200 mg twice a day.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (30 listed)

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of ≤ 1 within 14 days prior to registration. Cisplatin-ineligible chemotherapy-naïve subjects (see inclusion criteria #8) may have an ECOG Performance Status of ≤ 2.
Histological or cytological evidence/confirmation of urothelial cancer.
Metastatic and/or unresectable (cT4b) urothelial cancer.

Key exclusion criteria (17 listed)

Active infection requiring systemic therapy.
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Known additional malignancy that is active and/or progressive requiring treatment; subjects with other malignancies that have been definitively treated and who have been rendered disease free will be eligible.
Prior treatment with a PARP inhibitor, including olaparib.
Treatment with any investigational drug within 30 days prior to registration.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OlaparibAlso: Lynparza1 cycle = 28 days. Subject's with calculated creatinine clearance (CrCl) of ≥ 40 mL/min will start at a dose of olaparib tablets of 300 mg twice a day. Subjects with a CrCl of > 30 to < 40 mL/min will start at a dose of olaparib tablets 200 mg twice a day.	Drug	Olaparib Monotherapy

Primary outcome

Objective Response Rate (ORR)
Time frame: Up to a maximum of 17 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

1 secondary outcome

Progression-Free Survival (PFS)
Time frame: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 17 months.

Results and safety

Results posted to the registry on 22 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Olaparib Monotherapy	19	19

Primary outcome: Objective Response Rate (ORR)

Time frame: Up to a maximum of 17 months. Number. Unit: Percentage of participants

Measure	Olaparib Monotherapy n = 15
Value	0

Population analysed: Out of 19 patients, four subjects were not evaluable for best response.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: All-Cause Mortality was monitored up to a maximum of 23 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 18 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Olaparib Monotherapy	11 of 19 (57.9%)	18 of 19 (94.7%)	13 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Metastatic Urothelial Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 3
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Matthew Galsky, MD principal investigator

Mt Sinai School of Medicine

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaparib in people with Metastatic Urothelial Cancer, run by Matthew Galsky at 7 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 17 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: finished, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 22 Nov 2023). 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?

Objective Response Rate (ORR) (time frame: Up to a maximum of 17 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 NCT03448718.

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 22 Nov 2023.