Prostate Cancer MetastaticPhase 2TRIUMPHNCT03413995
Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations
A Phase 2 study testing Rucaparib in people with Prostate Cancer Metastatic, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
The aim of this research is to find out if the study drug rucaparib leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer Metastatic
- 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
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Sep 2018to 12 Sep 2024
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
- Males aged 18 years of age and above
- Histological or cytologic proof of adenocarcinoma of the prostate
- Germline mutation in one or more homologous recombination DNA-repair genes (BRCA1, BRCA2, ATM, CHEK2, NBN, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM) as documented by a clinical CLIA-grade, genetic test (including but not limited to Invitae, Color Genomics, etc)
- All patients must be ineligible for or have declined androgen deprivation therapy (ADT)-based systemic treatment
- Absolute PSA ≥2.0 ng/ml at screening.
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- Radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 8 weeks.
- Serum testosterone ≥ 100 ng/dl.
- Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
- Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT))
- Participants must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:
- Estimated creatinine clearance = (140-age [years]) x weight (kg) serum creatinine (mg/dL) x 72
- ECOG Performance Status <2
- Participants must have a life expectancy ≥ 12 months.
- Male participants and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see appendix E for acceptable methods], throughout the period of taking study treatment and for 6 months after last dose of study drug to prevent pregnancy in a partner.
Who cannot join
- Current active second malignancy (history of non-melanoma skin cancers and superficial bladder cancers are allowed)
- Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary is allowed; prior ADT for biochemical recurrence is also allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (>100 ng/dl). The total duration of prior ADT should not exceed 24 months.
- Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months is not permitted. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
- Presence of visceral (i.e. lung or liver) metastases >3cm in long-axis dimension.
- Pain due to bone metastases requiring narcotic analgesics.
- Prior treatment with intravenous chemotherapy.
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- Use of any prohibited concomitant medications (Appendix B: Medications With the Potential for Drug-Drug Interactions) within the prior 2 weeks.
- Involvement in the planning and/or conduct of the study (applies to both Clovis Oncology staff and/or staff at the study site)
- Previous enrollment in the present study
- Participation in another clinical study with an investigational product during the last 1 month.
- Any previous treatment with a PARP inhibitor, including rucaparib.
- Resting ECG with QTc > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
- Major surgery within 2 weeks of starting study treatment, and patients must have recovered from any effects of any major surgery.
- 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 6 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
- Unable to swallow orally administered medication or gastrointestinal disorders likely to interfere with absorption of the study medication.
- Immunocompromised patients, e.g., patients who are known to be serologically positive for HIV. Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
- Known hypersensitivity to rucaparib or any of the excipients of the product.
- Whole blood transfusions in the last 30 days prior to entry to the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21205
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: Phase II Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH)
The aim of this research is to find out if the study drug rucaparib leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene involved in repairing DNA damage. The research will also examine if rucaparib is safe in individuals with metastatic prostate cancer.
Prior research studies have shown that drugs like rucaparib can be of benefit to patients with advanced metastatic prostate cancer who are resistant to androgen deprivation therapy AND who carry a mutation in a DNA repair gene. We are studying if rucaparib will be an effective treatment for these patients earlier in their treatment course (for example, prior to the start of medicines that lower testosterone level). It is unknown whether rucaparib will have the same benefit in men with metastatic prostate cancer carrying a mutation in a DNA repair gene, prior to the use of medicines that lower your testosterone level.
Read the detailed description
With respect to germline mutations, a recent study found that the incidence of inherited DNA-repair gene alterations in metastatic prostate cancer to be significantly higher (11.8%) than in both men with localized prostate cancer (4.6%) and in the general population at large (2.7%). Specifically, mutations in 7 genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, RAD51D, GEN1) were significantly enriched in patients with metastatic prostate cancer compared to the general population. These findings suggest that a subset of men are more likely to develop metastatic prostate cancer (i.e. those with germline mutations in DNA-repair genes) and may potentially benefit from PARPi therapy.
The clinical activity of PARPi in patients with DNA-repair mutations and metastatic prostate cancer has now been established. Focusing specifically on patients with a germline mutation in a pre-specified group of DNA-repair genes, we hypothesize that targeted therapy with PARPi should be sufficient to induce a clinical response irrespective of hormonal (castration-sensitive or castration-resistant) status. Our hypothesis is based largely on the data from Mateo et al showing a clinical response rate of 88% in a heavily pre-treated population of mCRPC patients with a DNA repair mutation, with the most pronounced responses being in men with germline inactivation.
For men with mHSPC, this trial would also provide an alternative to ADT. Identification of a non-hormonal based therapy is warranted as ADT is associated with a shorter time to castration resistance in men harboring a germline DNA repair mutation versus those with intact DNA repair. However, given that primary ADT (in mHSPC) is a standard first-line therapy, all patients on trial must be ineligible for or decline standard-of-care hormonal treatment. For patients with mHSPC who do not respond to PARPi, we will build safety rules into the trial design to take patients off study at first signs of progression. Primary ADT (mHSPC) would still remain a treatment option upon progression.
- Conditions
- Prostate Cancer Metastatic
- Being tested
- Rucaparib
- Keywords
- metastatic hormone sensitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Continuous dosing
| Study group | Role | What they receive |
|---|---|---|
| Rucaparib 600 mg BID, continuous dosing | Experimental | Rucaparib 600mg by mouth twice daily, continuous dosing Receives: Drug: Rucaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Prostate Specific Antigen (PSA) >=50 Response
Response Rate(PSA) Prostate Specific Antigen to rucaparib for patients with metastatic hormone sensitive prostate cancer harboring germline mutation in homologous recombination DNA (Deoxyribonucleic acid) repair gene. Measured by decline in PSA to 50% of baseline, confirmed with second measurement at least 4 weeks apart.
Measured: 4 weeks
Secondary outcomes (4)
Number of Participants With Treatment-related Adverse Events
As assessed by CTCAE v4.0
Measured: 4 years 8 months
PSA Progression-free Survival
Defined as a time (months) from initiation of rucaparib therapy until PSA increase of 25 %, confirmed with another measurement at least 3 weeks later
Measured: 2 years
Progression-free Survival
Defined as time (months) from initiation of rucaparib therapy to radiographic or clinical progression or death, whichever comes first.
Measured: 2 years
Objective Response
Defined as patients achieving a complete or partial response in target lesions found on radiographic scans among patients who have measurable disease at baseline.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2018
- Study start10 Sep 2018
- Primary completion8 Nov 2023
- Study completion12 Sep 2024
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 (2)Papers the sponsor has linked to this study.
- Other trials for Prostate Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- 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
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- Mark Markowski, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03413995
- Sponsor's protocol ID
- J17187
- Other IDs
- IRB00156514
- Acronym
- TRIUMPH
- Status last verified
- Sep 2024
- First submitted
- 18 Jan 2018
- Last updated
- 16 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Markowski MC, Sternberg CN, Wang H, Wang T, Linville L, Marshall CH, Sullivan R, King S, Lotan TL, Antonarakis ES. TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations. Oncologist. 2024 Sep 6;29(9):794-800. doi: 10.1093/oncolo/oyae120.
PubMed 38885246Nientiedt C, Duensing A, Zschabitz S, Jager D, Hohenfellner M, Stenzinger A, Duensing S. PARP inhibition in prostate cancer. Genes Chromosomes Cancer. 2021 May;60(5):344-351. doi: 10.1002/gcc.22903. Epub 2020 Oct 28.
PubMed 33084183
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH)
- ClinicalTrials.gov ID
- NCT03413995
- Acronym / sponsor ID
- TRIUMPH / J17187
- Conditions
- Prostate Cancer Metastatic
- Keywords
- metastatic hormone sensitive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 8 Nov 2023 (actual)
- Study completion
- 12 Sep 2024 (actual)
- First posted
- 29 Jan 2018 (actual)
- Results
- Posted 16 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this research is to find out if the study drug rucaparib leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene involved in repairing DNA damage. The research will also examine if rucaparib is safe in individuals with metastatic prostate cancer.
Prior research studies have shown that drugs like rucaparib can be of benefit to patients with advanced metastatic prostate cancer who are resistant to androgen deprivation therapy AND who carry a mutation in a DNA repair gene. We are studying if rucaparib will be an effective treatment for these patients earlier in their treatment course (for example, prior to the start of medicines that lower testosterone level). It is unknown whether rucaparib will have the same benefit in men with metastatic prostate cancer carrying a mutation in a DNA repair gene, prior to the use of medicines that lower your testosterone level.
Detailed description
With respect to germline mutations, a recent study found that the incidence of inherited DNA-repair gene alterations in metastatic prostate cancer to be significantly higher (11.8%) than in both men with localized prostate cancer (4.6%) and in the general population at large (2.7%). Specifically, mutations in 7 genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, RAD51D, GEN1) were significantly enriched in patients with metastatic prostate cancer compared to the general population. These findings suggest that a subset of men are more likely to develop metastatic prostate cancer (i.e. those with germline mutations in DNA-repair genes) and may potentially benefit from PARPi therapy.
The clinical activity of PARPi in patients with DNA-repair mutations and metastatic prostate cancer has now been established. Focusing specifically on patients with a germline mutation in a pre-specified group of DNA-repair genes, we hypothesize that targeted therapy with PARPi should be sufficient to induce a clinical response irrespective of hormonal (castration-sensitive or castration-resistant) status. Our hypothesis is based largely on the data from Mateo et al showing a clinical response rate of 88% in a heavily pre-treated population of mCRPC patients with a DNA repair mutation, with the most pronounced responses being in men with germline inactivation.
For men with mHSPC, this trial would also provide an alternative to ADT. Identification of a non-hormonal based therapy is warranted as ADT is associated with a shorter time to castration resistance in men harboring a germline DNA repair mutation versus those with intact DNA repair. However, given that primary ADT (in mHSPC) is a standard first-line therapy, all patients on trial must be ineligible for or decline standard-of-care hormonal treatment. For patients with mHSPC who do not respond to PARPi, we will build safety rules into the trial design to take patients off study at first signs of progression. Primary ADT (mHSPC) would still remain a treatment option upon progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rucaparib 600 mg BID, continuous dosing | Experimental | Drug: RucaparibRucaparib 600mg by mouth twice daily, continuous dosing |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
- Males aged 18 years of age and above
- Histological or cytologic proof of adenocarcinoma of the prostate
- Germline mutation in one or more homologous recombination DNA-repair genes (BRCA1, BRCA2, ATM, CHEK2, NBN, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM) as documented by a clinical CLIA-grade, genetic test (including but not limited to Invitae, Color Genomics, etc)
- All patients must be ineligible for or have declined androgen deprivation therapy (ADT)-based systemic treatment
Key exclusion criteria (20 listed)
- Current active second malignancy (history of non-melanoma skin cancers and superficial bladder cancers are allowed)
- Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary is allowed; prior ADT for biochemical recurrence is also allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (>100 ng/dl). The total duration of prior ADT should not exceed 24 months.
- Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months is not permitted. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
- Presence of visceral (i.e. lung or liver) metastases >3cm in long-axis dimension.
- Pain due to bone metastases requiring narcotic analgesics.
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 |
|---|---|---|
| RucaparibContinuous dosing | Drug | Rucaparib 600 mg BID, continuous dosing |
Primary outcome
Number of Participants With Prostate Specific Antigen (PSA) >=50 Response
Time frame: 4 weeks
Response Rate(PSA) Prostate Specific Antigen to rucaparib for patients with metastatic hormone sensitive prostate cancer harboring germline mutation in homologous recombination DNA (Deoxyribonucleic acid) repair gene. Measured by decline in PSA to 50% of baseline, confirmed with second measurement at least 4 weeks apart.
4 secondary outcomes
Number of Participants With Treatment-related Adverse Events
Time frame: 4 years 8 months
PSA Progression-free Survival
Time frame: 2 years
Progression-free Survival
Time frame: 2 years
Objective Response
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38885246Markowski MC, Sternberg CN, Wang H, Wang T, Linville L, Marshall CH, Sullivan R, King S, Lotan TL, Antonarakis ES. TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations. Oncologist. 2024 Sep 6;29(9):794-800. doi: 10.1093/oncolo/oyae120.
- Derived from this study: PubMed 33084183Nientiedt C, Duensing A, Zschabitz S, Jager D, Hohenfellner M, Stenzinger A, Duensing S. PARP inhibition in prostate cancer. Genes Chromosomes Cancer. 2021 May;60(5):344-351. doi: 10.1002/gcc.22903. Epub 2020 Oct 28.
- Individual participant dataSharing planned: Undecided
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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.
Mark Markowski, MD principal investigator
Johns Hopkins University
2 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 Rucaparib in people with Prostate Cancer Metastatic, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 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 19 inclusion and 20 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 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 16 Oct 2024). 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?
Number of Participants With Prostate Specific Antigen (PSA) >=50 Response (time frame: 4 weeks). 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 NCT03413995, which also lists 2 linked publications.
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 16 Oct 2024.