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A phase 3, randomized, double-blind, placebo-controlled study of Talazoparib with Enzalutamide in metastatic castration-resistant prostate cancer (TALAPRO-2) - C3441021

Studio Clinico

Patologia: Carcinoma della prostata

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Histologically or cytologically confirmed adenocarcinoma of the prostate withoutsmall cell or signet cell features
- Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be < 4).
- For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status
- Consent to a saliva sample collection for a germline comparator unless prohibited by local regulations or ethics committee decision (optional for patients in Part 1).
- Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
- Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan.
- 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.
    - 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.
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Life expectancy ≥ 12 months as assessed by the investigator.
- Able to swallow the study drug and have no known intolerance to study drugs or excipients.
- Must agree to use a condom when having sex with a partner from the time of the first dose of study drug through 4 months after last dose of study treatment. Must also agree for female partner of childbearing potential to use an additional highly effective form of contraception from the time of the first dose of study treatment through 4 months after last dose of study treatment when having sex with a non pregnant female partner of childbearing potential.
- Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug.
- Evidence of a personally signed and dated informed consent document (and molecular prescreening consent if appropriate) indicating that the patient [or a legally acceptable representative/legal guardian] has been informed of all pertinent aspects of the study.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Criteri di esclusione: 

- Any prior systemic cancer treatment initiated in in the non metastatic CRPC and mCRPC disease state.
- Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
- Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.
- 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.
- 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).
- 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).
- 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).
- 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.
- Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or randomization (Part 2).
- Clinically significant cardiovascular disease
- Significant renal dysfunction as defined by any of the following laboratory abnormalities:
    - Renal: eGFR < 30 mL/min/1.73 m2 by the MDRD equation (available via www.mdrd.com).
    - Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) at screening.
- Significant hepatic dysfunction as defined by any of the following laboratory abnormalities on screening labs:
    - Total serum bilirubin >1.5 times the upper limit of normal (ULN) (>3 × ULN for patients with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
    - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times ULN (>5 × ULN if liver function abnormalities are due to hepatic metastasis).
    - Albumin <2.8 g/dL
- Absolute neutrophil count < 1500/µL, platelets < 100,000/µL, or hemoglobin < 9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology values at screening).
- Known or suspected brain metastasis or active leptomeningeal disease.
- Symptomatic or impending spinal cord compression or cauda equina syndrome.
- History of another cancer including myelodysplastic syndrome or acute myeloid leukemia, with the exception of uncomplicated nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor
- Gastrointestinal disorder affecting absorption.
- Fertile male subjects who are unwilling or unable to use highly effective methods of contraception for the duration of the study and for 4 months after the last dose of investigational product.
- Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
- Other acute or chronic medical (concurrent disease, infection, or comorbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that interferes with ability to participate in the study, may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of randomization (Part 2).

Schema di trattamento: 

Talazoparib 0.5 mg/day plus Enzalutamide 160mg/day
Placebo plus Enzalutamide 160 mg/day

Trattamento sperimentale: 

Talazoparib+Enzalutamide

Trattamento di controllo: 

Placebo+Enzalutamide

Obiettivi primari dello studio: 

- Confirm the dose of Talazoparib (part 1) [Time Frame: Day 1 up to 28 days]
determined based on the safety profile

- Radiographic PFS (part 2) in unselected patients and in patients harboring DDR deficiencies [Time Frame: randomization up to 25 months]
time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death (occurring within 168 days of treatment discontinuation), whichever occurs first

Note generali: 

ll tessuto è richiesto solo per i pazienti arruolati nella parte 2 dello studio (Double-Blind Treatment). E' opzionale per i pazienti arruolati nella parte 1 (Open-Label Treatment)

Centri partecipanti

Nord Italia

Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO

Riferimento: Dr. Francesco Massari
Email: francesco.massari@aosp.bo.it

 

Azienda Spedali Civili di Brescia
Piazzale Spedali Civili 1 - 25123 Brescia - BS

Riferimento: Dr.ssa Francesca Valcamonico
Email: oncologia@asst-spedalicivili.it

 

ASST di Cremona
Viale Concordia 1 - 26100 Cremona - CR

Riferimento: Dr. Rodolfo Passalacqua
Telefono: 0372405242
Email: r.passalacqua@asst-cremona.it

 

IRCCS - IRST
Via P. Maroncelli 40 - 47014 Meldola - FC

Riferimento: Dr. Ugo De Giorgi

 

A.O.U San Luigi Gonzaga
Regione Gonzole 10 - 10043 Orbassano - TO

Riferimento: Dr.ssa Consuelo Buttigliero
Telefono: 0119026334
Email: consuelo.buttigliero@unito.it

 

Presidio ospedaliero di Santa Chiara
Largo Medaglie d'Oro 1 - 38122 Trento - TN

Riferimento: Caffo
Telefono: 0461902478
Email: orazio.caffo@apss.tn.it

 

Centro Italia

AOU Pisana - Santa Chiara
Via Roma 67 - 56126 Pisa - PI
U.O. Oncologia Medica 2

Riferimento: Dr. Luca Galli
Telefono: 050992466
Email: l.galli@ao-pisa.toscana.it

 

AO S. Maria Terni
Via Tristano di Joannuccio 1 - 05100 Terni - TR

Riferimento: Dr.ssa Claudia Caserta

 

Sud Italia e isole

AORN Cardarelli
Via A Cardarelli 9 - 80131 napoli - NA

Riferimento: Prof. Giacomo Cartenì
Telefono: 0817472221
Email: cartenigiacomo@gmail.com

 

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA

Riferimento: Dr. Gaetano Facchini
Telefono: 0815903637

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2017-003295-31

Data di inserimento: 29.01.2019

Promotore

Pfizer

CRO

/

Principal Investigator ITALIA

AOU San Luigi Gonzaga, Orbassano (TO)

Riferimento: Dr.ssa Consuelo Buttigliero

Telefono: 0119026334

Email: consuelo.buttigliero@unito.it

Localita: Orbassano (TO)

 

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