Bladder CancerPhase 2ATLASNCT03397394

Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 2 study testing Rucaparib in people with Bladder Cancer and Urothelial Carcinoma, run by pharmaand GmbH at 64 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma
What is being tested?: Rucaparib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 97 participants
Where: 64 sitesin 6 countries
Study dates: 1 Jun 2018to 15 Jan 2020
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

Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
Received 1 or 2 prior treatment regimens for advanced or metastatic disease
Confirmed radiologic disease progression during or following recent treatment
Mandatory biopsy is required during screening
Measurable disease per RECIST v1.1
Adequate organ function
ECOG 0 or 1

Who cannot join

Prior treatment with a PARP inhibitor
Symptomatic and/or untreated CNS metastases
Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

Trial locations and contacts

64 sites in 6 countries.

Country

City, postcode or hospital

64 sites in 6 countries

United States41 sites

New York Oncology Hematology, P.C. (USO - US Oncology)
Albany, New York, 12208
University of New Mexico UNM Cancer Research and Treatment Center
Albuquerque, New Mexico, 87102
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103
University of Michigan
Ann Arbor, Michigan, 48109
University of Maryland, Marlene and Stewart Greenebaum Cancer Center
Baltimore, Maryland, 21201
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Virginia, Emily Couric Clinical Center
Charlottesville, Virginia, 22908
University Oncology & Hematology
Chattanooga, Tennessee, 37403
Northwestern University, Chicago
Chicago, Illinois, 60611
Texas Oncology PA (USO - US Oncology)
Dallas, Texas, 76201
Duke University, Duke Cancer Institute
Durham, North Carolina, 27710
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Hartford Health Care Cancer Institute
Hartford, Connecticut, 06102
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Texas, UT Health Science Center
Houston, Texas, 77030
Indiana University - Melvin and Bren Simon Cancer Center (IUSCC)
Indianapolis, Indiana, 46202
The University of Iowa and Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of California San Diego (UCSD), Moores Cancer Center
La Jolla, California, 92093
Comprehensive Cancer Centers of Nevada (CCCN)
Las Vegas, Nevada, 89169
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
Norton Cancer Center
Louisville, Kentucky, 40207
Miami Cancer Institute, Baptist Health South Florida
Miami, Florida, 33176
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Minnesota Oncology Hematology P.A. (USO - US Oncology)
Minneapolis, Minnesota, 55404
Atlantic Urology Clinics
Myrtle Beach, South Carolina, 29572
Urology Associates
Nashville, Tennessee, 37209
Ochsner Cancer Institute
New Orleans, Louisiana, 70121
New York - Presbyterian Hospital-Weill Cornell Medical Center
New York, New York, 10021
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Eastern Connecticut Hematology & Oncology Associates (ECHO)
Norwich, Connecticut, 06360
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Universityof California, Irvine
Orange, California, 92868
Northwest Cancer Specialists P.C. (USO - US Oncology)
Portland, Oregon, 97062
Providence Portland Medical Center
Portland, Oregon, 97213
Oregon Health and Science University
Portland, Oregon, 97239
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Saint John's Health Center - John Wayne Cancer Institute (JWCI)
Santa Monica, California, 90404
Pinnacle Oncology, Honor Health
Scottsdale, Arizona, 85258
University of Washington / Seattle Cancer Care Alliance
Seattle, Washington, 98109
Stanford University School of Medicine
Stanford, California, 94304
Medstar Georgetown University Medical Center
Washington D.C., District of Columbia, 20007

Other trials in United States

Spain9 sites

Hospital del Mar
Barcelona, 08003
Hospital Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitari Vall d'Hebron de Barcelona
Barcelona, 08035
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Clinica Universitaria de Navarra Madrid
Madrid, 28027
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario 12 de Octubre
Madrid, 28041
Universidad de Navarra - Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, 15706

Other trials in Spain

France5 sites

Centre de Lutte Contre le Cancer (CLCC) - Universite de Lyon - Centre Leon-Berard
Lyon, 69008
Hopital Saint-Louis
Paris, 75010
Centre de Lutte Contre le Cancer - Institut de Cancerologie de l'Ouest - Rene Gauducheau
Saint-Herblain, 44805
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94805

Other trials in France

Italy4 sites

Fondazionerca sul Cancro ONLUS - Istituto di Candiolo IRCCS
Candiolo, 10060
IRCCS Ospedale San Raffaele - Medical Oncology Dept
Milan, 20132
Fondazione IRCCS Istituto Nazionale Tumori
Milan, 20133
Azienda Ospedaliera Universitaria Federico II Oncologia Medica
Naples, 80131

Other trials in Italy

Germany3 sites

Urologische und Kinderurologische Universitätsklinik im Malteser
Erlangen, 91054
Universitatsklinikum Munster / Urologie und Kinderurologie
Münster, 26133
Studienpraxis Urologie
Nürtingen, 72622

Other trials in Germany

United Kingdom2 sites

Sarah Cannon Research Institute - United Kingdom - London Office
London, CH63 4JY
Guy's & St. Thomas' Hospital (London Oncology Clinic)
London, W1G 6AF

Other trials in United Kingdom

About this study

Official title: A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Conditions: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Renal Pelvis Carcinoma, Ureter Carcinoma, Urinary Bladder Carcinoma
Being tested: Rucaparib
Keywords: PARP inhibitor, PARPi, HRD, ATLAS, homologous recombination, DNA repair, LOH, DNA defect, DNA anomaly, Rucaparib, MIBC
Medical subject headings: Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Ureteral Neoplasms, Urethral Neoplasms

What participants receive

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

RucaparibDrug
Also called CO-338
Rucaparib will be administered daily.

Study groups in NCT03397394
Study group	Role	What they receive
Rucaparib	Experimental	Oral rucaparib (monotherapy) Receives: Drug: Rucaparib

What is being measured

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

Objective Response Rate (ORR) Per RECIST Version 1.1
ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR), is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Measured: Time from first dose to date of progression, up to approximately 19 months

Secondary outcomes (3)

Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator
PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.
Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 10 months
Overall Survival
Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure).
Measured: The total study time for reporting of deaths was approximately 19 months.
Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations
Plasma were collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1.
Measured: From Cycle 2 Day 1 to Cycle 4 Day 1, or approximately 2 months

Timeline

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

1 Jun 201815 Jan 2020

First posted12 Jan 2018
Study start1 Jun 2018
Primary completion12 Dec 2019
Study completion15 Jan 2020

Why it stopped: Efficacy did not meet the continuance criteria and DMC recommended to stop enrollment.

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Bladder 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: 97 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03397394
Sponsor's protocol ID: CO-338-085
Other IDs: 2017-004166-10, 2017
Acronym: ATLAS
Status last verified: Jun 2023
First submitted: 21 Dec 2017
Last updated: 9 Jun 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Grivas P, Loriot Y, Morales-Barrera R, Teo MY, Zakharia Y, Feyerabend S, Vogelzang NJ, Grande E, Adra N, Alva A, Necchi A, Rodriguez-Vida A, Gupta S, Josephs DH, Srinivas S, Wride K, Thomas D, Simmons A, Loehr A, Dusek RL, Nepert D, Chowdhury S. Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS). BMC Cancer. 2021 May 24;21(1):593. doi: 10.1186/s12885-021-08085-z.
PubMed 34030643

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 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
RecruitingPhase 3
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)
Bladder Cancer
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma

All Bladder Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
ClinicalTrials.gov ID: NCT03397394
Acronym / sponsor ID: ATLAS / CO-338-085
Conditions: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Renal Pelvis Carcinoma, Ureter Carcinoma, Urinary Bladder Carcinoma
Keywords: PARP inhibitor, PARPi, HRD, ATLAS, homologous recombination, DNA repair, LOH, DNA defect
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Efficacy did not meet the continuance criteria and DMC recommended to stop enrollment.
Enrolment: 97 participants (actual)
Lead sponsor: pharmaand GmbHIndustry (pharma, biotech, devices)
Collaborators: Foundation Medicine
Study start: 1 Jun 2018 (actual)
Primary completion: 12 Dec 2019 (actual)
Study completion: 15 Jan 2020 (actual)
First posted: 12 Jan 2018 (actual)
Results: Posted 19 Oct 2020

Clinical summary

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

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Study design

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

Arm	Type	Receives
Rucaparib	Experimental	Drug: RucaparibOral rucaparib (monotherapy)

Who may qualify

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

Key inclusion criteria (7 listed)

Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
Received 1 or 2 prior treatment regimens for advanced or metastatic disease
Confirmed radiologic disease progression during or following recent treatment
Mandatory biopsy is required during screening
Measurable disease per RECIST v1.1

Key exclusion criteria (3 listed)

Prior treatment with a PARP inhibitor
Symptomatic and/or untreated CNS metastases
Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

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
RucaparibAlso: CO-338Rucaparib will be administered daily.	Drug	Rucaparib

Primary outcome

Objective Response Rate (ORR) Per RECIST Version 1.1
Time frame: Time from first dose to date of progression, up to approximately 19 months
ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR), is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

3 secondary outcomes

Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator
Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 10 months
Overall Survival
Time frame: The total study time for reporting of deaths was approximately 19 months.
Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations
Time frame: From Cycle 2 Day 1 to Cycle 4 Day 1, or approximately 2 months

Results and safety

Results posted to the registry on 19 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HRD Unknown	47	47
HRD Negative	30	30
HRD Positive	20	20

Primary outcome: Objective Response Rate (ORR) Per RECIST Version 1.1

Time frame: Time from first dose to date of progression, up to approximately 19 months. Count of participants. Unit: Participants

Measure	HRD Unknown n = 47	HRD Negative n = 29	HRD Positive n = 19	Overall n = 95
Value	0	0	0	0

Population analysed: Intent-to-treat Population (ITT) with measurable disease at Baseline - The ITT population includes all patients who received at least 1 dose of rucaparib. One patient each in the HRD negative and HRD positive groups did not have measurable disease at Baseline.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events for each patient were reported from the first dose until 28 days after last dose of study drug, and the total study time for adverse event reporting was approximately 19 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HRD Unknown	20 of 47 (42.6%)	45 of 47 (95.7%)	9 of 47
HRD Negative	14 of 30 (46.7%)	29 of 30 (96.7%)	8 of 30
HRD Positive	11 of 20 (55%)	19 of 20 (95%)	7 of 20
Overall	45 of 97 (46.4%)	93 of 97 (95.9%)	24 of 97

Limitations and caveats (from the sponsor): The study was terminated early based on an interim analysis by the Data Monitoring Committee that demonstrated that ORR did not meet the protocol-defined continuance criteria. There were no confirmed responses observed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34030643Grivas P, Loriot Y, Morales-Barrera R, Teo MY, Zakharia Y, Feyerabend S, Vogelzang NJ, Grande E, Adra N, Alva A, Necchi A, Rodriguez-Vida A, Gupta S, Josephs DH, Srinivas S, Wride K, Thomas D, Simmons A, Loehr A, Dusek RL, Nepert D, Chowdhury S. Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS). BMC Cancer. 2021 May 24;21(1):593. doi: 10.1186/s12885-021-08085-z.

Related trials for Bladder Cancer

RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
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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.

The record lists no contact. Use the official record to reach the sponsor.

64 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rucaparib in people with Bladder Cancer and Urothelial Carcinoma, run by pharmaand GmbH at 64 sites in 6 countries.

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 7 inclusion and 3 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: stopped early, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Spain, France, Italy, Germany and 1 more country. 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 19 Oct 2020). 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) Per RECIST Version 1.1 (time frame: Time from first dose to date of progression, up to approximately 19 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 NCT03397394, which also lists 1 linked publication.

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 9 Jun 2023.