Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03413995|
Recruitment Status : Recruiting
First Posted : January 29, 2018
Last Update Posted : February 11, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer Metastatic||Drug: Rucaparib||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH)|
|Actual Study Start Date :||September 10, 2018|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||November 2021|
Experimental: Rucaparib 600 mg BID, continuous dosing
Rucaparib 600mg by mouth twice daily, continuous dosing
- Response Rate(PSA)to rucaparib for pts with met. hormone sensitive prostate ca harboring germline mutation in homologous recombination DNA repair gene. Measured by decline in PSA to 50% of baseline, confirmed w/second measurement at least 4 weeks apart. [ Time Frame: 4 weeks ]
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
- PSA progression-free survival, defined as a time from initiation of rucaparib therapy until PSA increase of 25 %, confirmed with another measurement at least 3 weeks later [ Time Frame: 6 months ]
- Progression-free survival, defined as time from initiation of rucaparib therapy to radiographic or clinical progression or death, whichever comes first. [ Time Frame: 2 years ]
- Objective response rate, defined as the proportion of patients achieving a complete or partial response in target lesions found on radiographic scans [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03413995
|Contact: Mark Markowski, MDemail@example.com|
|Contact: Rana Sullivan, RNfirstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Rana Sullivan, RN 410-614-6337 email@example.com|
|Principal Investigator: Mark Markowski, MD|
|Principal Investigator:||Mark Markowski, MD||Johns Hopkins University|