NCT03148795已完成2 期
TALAPRO-1: A PHASE 2, OPEN-LABEL, RESPONSE RATE STUDY OF TALAZOPARIB IN MEN WITH DNA REPAIR DEFECTS AND METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO PREVIOUSLY RECEIVED TAXANE-BASED CHEMOTHERAPY AND PROGRESSED ON AT LEAST 1 NOVEL HORMONAL AGENT (ENZALUTAMIDE AND/OR ABIRATERONE ACETATE/PREDNISONE)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 128
- 试验地点
- 118
- 主要终点
- Best Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age.
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features.
- •Patients must have measurable soft tissue disease per RECIST 1.1
- •DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel (testing of de novo or archival tumor tissue (via central laboratory) or prior historical testing (with Sponsor approval) using the Foundation Medicine, FoundationOne CDx™ NGS gene panel test.
- •Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
- •Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.
- •Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).
- •Progressive disease at study entry defined as 1 or more of the following 3 criteria:
- •A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be ≥ 2 μg/L (2 ng/mL) if qualifying solely by PSA progression.
- •Soft tissue disease progression as defined by RECIST 1.
- •Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan.
- •Metastatic disease.
- •Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies.
- •Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC.
- •Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Estimated life expectancy of ≥ 6 months as assessed by the investigator.
- •Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements.
- •Must use a condom when having sex from the time of the first dose of study drug through 4 months after last dose of study drug. A highly effective form of contraception must be used from the time of the first dose of study drug through 4 months after last dose of study drug 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.
- •Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
排除标准
- •Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day
- •Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy <=6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded.
- •Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within 4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during study participation
- •Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day
- •Major surgery within 2 weeks before day
- •Clinically significant cardiovascular disease.
- •Significant renal, hepatic, or bone marrow organ dysfunction.
- •Known or suspected brain metastasis or active leptomeningeal disease.
- •Symptomatic or impending spinal cord compression or cauda equina syndrome.
- •Prior diagnosis of myelodysplastic syndrome or acute myeloid leukemia
- •History of another cancer within 3 years before enrollment with the exception of 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.
- •Current or anticipated use within 7 days prior to first dose of study drug or anticipated use during the study of the following 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).
- •Any other acute or chronic medical or psychiatric condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of data, in the opinion of the investigator or sponsor, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that 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.
- •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.
- •Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 4 months after the last dose of investigational product.
研究组 & 干预措施
Talazoparib
Experimental
Talazoparib 1 mg daily
干预措施: Talazoparib (Drug)
结局指标
主要结局
Best Objective Response Rate (ORR)
时间窗: From first dose of study drug to best overall soft tissue response CR or PR (maximum duration of 25 months)
Best ORR was defined as the percentage of participants with best overall soft tissue response of complete response (CR) or partial response (PR) as per RECIST1.1 by an independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 millimeter (mm). Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
次要结局
- Time to Objective Response(From first dose of study drug to first objective response (maximum duration of 25 months))
- Percentage of Participants With a Null CTC Count(Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months)
- Percentage of Participants With Baseline CTC Count <5 CTC Showed Increased CTC Counts at Any Time on Study(Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months)
- Percentage of Participants With Conversion of Circulating Tumor Cell (CTC) Count(Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months)
- Number of Participants With Clinically Significant Abnormalities in Vital Signs(During study treatment (approximately up to 36 months))
- Number of Participants With Dose Modification(During study treatment (approximately up to 36 months))
- Duration of Response (DOR)(From the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first (maximum duration of 25 months))
- Percentage of Participants With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percentage (%)(From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months))
- Time to Prostate-Specific Antigen (PSA) Progression(From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months))
- Radiographic Progression-Free Survival (PFS)(From date of first dose of study drug to first objective evidence of radiographic progression or death without documented radiographic progression, whichever occurs first (maximum duration of 25 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(First dose of study drug up to 28 days after last dose of study drug (study treatment was approximately for 36 months, safety follow up to approximately 37 months))
- Number of Participants With Permanent Treatment Discontinuation Due to Adverse Events(During study treatment (approximately up to 36 months))
- Number of Participants With Shift in Laboratory Parameter Values (Chemistry) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline(During study treatment (approximately up to 36 months))
- Time to Deterioration in Pain Symptom Scores(Baseline till final analysis of the outcome measure, up to maximum duration of 25 months)
- Number of Participants With 5 Response Levels for EQ-5D-5L Pain and Discomfort Domain(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Change From Baseline in European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L) Visual Analogue Scores (VAS)(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Number of Participants With 5 Response Levels for EQ-5D-5L Self-Care Domain(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Number of Participants With 5 Response Levels for EQ-5D-5L Usual Activity Domain(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Overall Survival (OS)(From first dose of study treatment up to death due to any cause during study or date of last contact (approximately 36 months))
- Number of Participants With Shift in Laboratory Parameter Values (Hematology) From Grade Less Than Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-baseline(During study treatment (approximately up to 36 months))
- Pre-dose Plasma Concentration (Ctrough) of Talazoparib(Pre-dose at Week 1, 5, 9 and 13)
- Change From Baseline in Participant Reported Pain Scores Per BPI-SF Question 3(Baseline, Week 1, 3, 5, 7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Number of Participants With 5 Response Levels for EQ-5D-5L Mobility Domain(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Number of Participants With 5 Response Levels for EQ-5D-5L Anxiety and Depression Domain(Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months])
- Post-dose Plasma Concentration (Ctrough) of Talazoparib(2 hours post-dose at Week 1 and 5)
研究者
研究点 (118)
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