Study Of Talazoparib With Enzalutamide In Metastatic Castration-resistant Prostate Cancer
- Conditions
- Metastatic Castration-resistant Prostate CancerMedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003295-31-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 872
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. At least 18 years of age. For Japan, at least 20 years of age.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features. If the patient does not have a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis and to support biomarker analysis.
3. Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be <4).
4. For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status by prospective analysis (de novo or archival tissue), or historical analysis (with Sponsor pre-approval), of most recent tumor tissue per FoundationOne testing. (Note: for patients enrolling in Part 1, DDR deficiency testing is optional).
5. For enrollment into Part 2 only (optional for Part 1): Unless prohibited by local regulations or ethics committee decision, consent to a saliva sample collection for retrospective sequencing of the same DDR genes tested on tumor tissue, or a subset thereof, and to serve as a germline control in identifying tumor mutations.
6. Surgically or medically castrated, with serum testosterone =50 ng/dL (=1.73 nmol/L) at screening. Or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist for patients who have not undergone bilateral orchiectomy must be initiated at least 4 weeks before Day 1 (Part 1) or randomization (Part 2) and must continue throughout the study.
7. Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan. Scans obtained as part of standard of care in the 6 weeks (42 days) prior to Day 1 (Part 1) or randomization (Part 2) can be used if they meet study requirements (Table 2). Measurable soft tissue disease is not required. (Adenopathy below the aortic bifurcation alone does not qualify).
8. Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria:
- Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 consecutive assessments with an interval of at least 7 days between assessments. The screening laboratory PSA value must be =2 ?g/L (=2 ng/mL) if qualifying solely by PSA progression.
- Soft tissue disease progression as defined by RECIST 1.1.
- Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan.
9. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before Day 1 (Part 1) or randomization (Part 2) for patients receiving these therapies.
10. Eastern Cooperative Oncology Group (ECOG) performance status =1.
11. Life expectancy ?12 months as assessed by the investigator.
12. Able to swallow the study treatment and have no known intolerance to study treatments or excipients.
13. Sexually active participants that in the opinion of the investigator are capable of ejaculating, must agree to use a condom when having sex with a partn
Patients with any of the following characteristics/conditions will be excluded:
1. Any prior systemic cancer treatment initiated in the non-metastatic CRPC and mCRPC disease state. This includes prior treatment with taxane-based chemotherapy or NHT of enzalutamide, apalutamide, or darolutamide initiated after onset of castration resistance setting.
2. Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
3. Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.
4. Prior treatment with platinum-based chemotherapy within 6 months prior to Day 1 (Part 1) or randomization (Part 2), or any history of disease progression on platinum-based therapy at any time in the past.
5. Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel-T (other than approved bone-targeting agents and GnRH agonist/antagonist therapy), or radionuclide therapy in the 28 days prior to Day 1 (Part 1) or randomization (Part 2). Hormonal therapy (eg, bicalutamide, nilutamide, flutamide, estrogens, 5 alpha reductase inhibitors are not exclusionary if discontinued prior to randomization. *Corticosteroid use of >10 mg/day is exclusionary. (The concomitant use of systemic glucocorticoid administration such as stress dose” glucocorticoid is permitted when clinically indicated for a life threatening medical condition).
6. Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug (whichever is longer) before Day 1 (Part 1) or randomization (Part 2).
7. Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization
(Part 2) unless no pain related to prostate cancer has been reported in the 28 days prior to Day 1 (Part 1) or randomization (Part 2).
8. Current use within 7 days prior to Day 1 (Part 1) or randomization (Part 2) or anticipated use during the study of the following medications:
- Potential DDI with talazoparib: P-gp inhibitors (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar).
- Potential DDI with enzalutamide: strong cytochrome P450 2C8 (CYP2C8) inducers (eg, rifampin), strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin and rifapentine), moderate CYP3A4 inducers (eg, bosentan, efavirenz, etravirine, modafinil and nafcillin), and substrates of CYP3A4 (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (eg, phenytoin), or CYP2C19 (eg, S mephenytoin) with a narrow therapeutic index.
9. Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or randomization (Part 2).
10. Clinically significant cardiovascular disease, including any of the following:
- Myocardial infarction or symptomatic cardiac ischemia within 6 months before Day 1 (Part 1) or randomization (Part 2).
- Congestive heart failure New York Heart Association class III or IV.
- History of clinically s
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method