Talazoparib Plus Enzalutamide After Progression to Prior ARPi in Metastatic Prostate Cancer (TEAM PC)
A Multicenter, Open Label, Randomized Phase II Trial to Evaluate the Efficacy of Talazoparib Plus Enzalutamide as First Line Treatment for Patients With Metastatic Castration Resistant Prostate Cancer After Progression to an Androgen Receptor Pathway Inhibitor
The purpose of this clinical trial is to determine the anti-tumor activity of talazoparib plus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed on Androgen Receptor Pathway Inhibitor (ARPI).
The main questions it aims to answer are:
- Does talazoparib plus enzalutamide improve efficacy in metastatic castration resistant prostate cancer (mCRPC) compared to enzalutamide alone?
- What is the time to disease progression [radiographic, Prostate Specific Antigen (PSA), clinical] in participants treated with talazoparib plus enzalutamide after progression on abiraterone?
- What medical problems do participants have when receiving talazoparib plus enzalutamide?
Researchers will compare the combination of talazoparib and enzalutamide as a first-line treatment for mCRPC to see if the combination improves the PSA response rate and delays progression compared to enzalutamide alone. The safety and tolerability of the combination (talazoparib and enzalutamide) will also be studied
연구 개요
상태
정황
상세 설명
This is a multicenter, open-label, randomized, phase II trial to evaluate the efficacy of the combination of talazoparib plus enzalutamide versus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed to abiraterone or other androgen receptor inhibitors (ARi) based treatment for metastatic hormone sensitive prostate cancer (mHSPC). Participants who meet the eligibility criteria will be randomized 2:1 to the experimental arm (enzalutamide and talazoparib) or control arm (enzalutamide) and will receive treatment until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
The experimental arm will be evaluated as 2 separate arms, post-AA and post-ARi, each with a single-stage phase II trial design. The control arm will not be directly compared to the experimental arm but will be used to explore biomarker differences in outcome measures between the experimental and control arm and confirm the statistical assumptions for the response rate under the null hypothesis.
Prostate cancer is the second most common malignancy in men worldwide with an estimated annual global incidence of 1.3 million and over 375,000 deaths. Aggressive variant prostate cancer is a clinically defined subset of metastatic castration resistant prostate cancers (mCRPC) characterized by the absence of response to androgen receptor (AR) targeted agents and neuroendocrine features. The treatments that are currently available are not effective, representing an unmet clinical need. The combination of talazoparib, a potent selective PARP inhibitor (PARPi) and enzalutamide (androgen receptor signaling inhibitor; ARPi) demonstrated in the TALAPRO-2 study improved efficacy in metastatic castration resistant prostate cancer (mCRPC) participants with and without DNA damage response (DDR) gene alterations as first line treatment (1L) compared to enzalutamide alone.
Estimated duration of the study: 48 months. Accrual is expected to be completed in 30 months. Median treatment duration has been estimated in 10 months. After completion of (or discontinuation from) treatment, participants will be followed up for survival until end of study (EoS) that will occur at 18 months after the enrollment of the last patient included in the trial, unless premature termination of the study.
It is hypothesized that after progression to abiraterone, the addition of talazoparib to enzalutamide as 1L for mCRPC will result in improved PSA response rate and delayed progression compared to enzalutamide alone.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Luis Gonzaga Paz-Ares Rodríguez
- 전화번호: +34 91 560 82 27
- 이메일: info@oncosur.org
연구 연락처 백업
- 이름: Elena Castro, Dra.
- 전화번호: +34 91 560 82 27
- 이메일: ecastro.imas12@h12o.es
연구 장소
-
-
-
Madrid, 스페인
- 아직 모집하지 않음
- Hospital Fundación Jiménez Díaz
-
연락하다:
- Imanol Martínez Salas
-
-
Barcelona
-
Badalona, Barcelona, 스페인, 08916
- 모병
- Institut Català d'Oncologia (ICO)
-
연락하다:
- María Ochoa de Olza
-
Barcelona, Barcelona, 스페인, 08003
- 모병
- Hospital del Mar
-
연락하다:
- Alejo Rodriguez-Vida, Dr.
-
Barcelona, Barcelona, 스페인, 08036
- 모병
- Hospital Clínico y Provincial de Barcelona
-
연락하다:
- Begoña Mellado, Dra.
-
Sabadell, Barcelona, 스페인, 08208
- 모병
- Consorcio Corporación Sanitaria Parc Taulí
-
연락하다:
- Enrique Gallardo, Dr.
-
-
Cantabria
-
Santander, Cantabria, 스페인, 39008
- 모병
- Hospital Universitario Marqués de Valdecilla
-
연락하다:
- Ignacio Duran, Dr.
-
-
Cádiz
-
Cadiz, Cádiz, 스페인, 11407
- 빼는
- Hospital Universitario de Jerez de la Frontera
-
-
Madrid
-
Madrid, Madrid, 스페인, 28046
- 모병
- Hospital Universitario La Paz
-
연락하다:
- Estefania Linares, Dra.
-
Madrid, Madrid, 스페인, 28041
- 모병
- Hospital 12 de Octubre
-
연락하다:
- Elena Castro, Dra.
-
Madrid, Madrid, 스페인, 28040
- 빼는
- Hospital Clínico San Carlos
-
-
Málaga
-
Málaga, Málaga, 스페인, 29010
- 모병
- Hospital Universitario Virgen de la Victoria
-
연락하다:
- Bernardo Herrera, Dr.
-
-
Vizcaya
-
Barakaldo, Vizcaya, 스페인, 48903
- 모병
- Hospital Universitario Cruces
-
연락하다:
- Eneko Novo Sukia, Dr.
-
-
Zaragoza
-
Zaragoza, Zaragoza, 스페인, 50009,
- 모병
- Hospital Universitario Miguel Servet
-
연락하다:
- Ángel Borque, Dr.
-
-
-
-
-
Bordeaux, 프랑스
- 모병
- Institut Bergonié
-
연락하다:
- Guilhem Roubaud
-
Brest, 프랑스
- 모병
- Hôpital Universitaire de Brest
-
연락하다:
- Benjamin Auberger
-
Lille, 프랑스
- 아직 모집하지 않음
- Centre Oscar Lambret
-
연락하다:
- Yaovi Eric Amela
-
Paris, 프랑스
- 모병
- Hôpital Saint Joseph
-
연락하다:
- Carole Helissey
-
Strasbourg, 프랑스
- 모병
- Hôpitaux Universitaire de Strasbourg
-
연락하다:
- Philippe Barthelemy
-
Villejuif, 프랑스
- 모병
- Institut Gustave Roussy
-
연락하다:
- Anna Patrikidou
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Male age 18 or older.
- Histological diagnosis of prostate adenocarcinoma without neuroendocrine differentiation or small cell features.
- Willing and able to provide written informed consent to participate in the study. Written consent must be given before registration, according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) / Good clinical practice (GCP), and national/local regulations.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Willing to provide tumor biopsies during the study. Note: At study entry, the pre-treatment new tumor biopsy (fresh-frozen and Formalin-fixed and paraffin-embedded (FFPE) material) could be replaced by an archived tumor biopsy upon agreement from the study chief investigator if such biopsy has been taken after progression to metastatic castration resistance and has both archived fresh-frozen material and a FFPE block with a minimum tumor content over 30 percent. Still the patient must be amenable and willing to undergo a new mandatory post-treatment biopsy.
- Willing to provide blood samples for biomarker analysis.
- Willing to give consent to sequencing of DNA damage repair (DDR) genes for analysis of the prevalence of somatic and germline aberrations in DNA damage repair genes.
- Metastatic (M1) prostate cancer documented by bone scan, or soft tissue disease documented by computed tomography (CT), or magnetic resonance imaging (MRI).
- Asymptomatic or minimally symptomatic prostate cancer at screening.
- Estimated life expectancy of greater than or equal to 6 months from screening.
- Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist or antagonist for participants who have not undergone bilateral orchiectomy must be in place before screening and must continue throughout the study.
12 .Disease progression after at least 12 weeks of treatment with a prior androgen-receptor signalling inhibitor (ARPi), including abiraterone acetate or a direct AR inhibitor, such as enzalutamide, apalutamide, or darolutamide, for metastatic hormone-sensitive prostate cancer. Note: Patients who previously received Enzalutamide can be recruited but up to a maximum of 6. Those patients will be included directly into the experimental arm. Progression is defined as:
a. PSA rise of greater than or equal to 25 percent and an absolute increase of greater than or equal to 2 ng/mL above nadir (or baseline for participants with no PSA decline), confirmed by a second PSA value at least 3 weeks later.
and / or b. Limited radiographic progression: maximum of 2 new bone metastases, no new soft tissue metastasis and less than 50 percent increase in the size of measurable soft tissue lesions.
13. Participants who have received prior docetaxel must meet the following criteria:
a. Received a maximum of 6 cycles of docetaxel for mHSPC and b. Received the last dose of docetaxel equal or higher than 6 months prior to randomization.
14. Participants who have received prior Lu177-PSMA must meet the following criteria:
a. Received a maximum of 6 cycles of docetaxel for mHSPC. b. Received the last dose of Lu177-PSMA equal or higher than 6 months prior to randomization 15. Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:
-
Haemoglobin greater than or equal to 10 g/dL, no blood transfusions within 14 days before obtaining the haematology laboratory tests at screening,
-
Platelets greater than or equal to 100,000/μL no platelets transfusions within 14 days before obtaining the haematology laboratory tests at screening,
-
Neutrophils greater than or equal to 1500/μL, no growth factors given within 14 days before obtaining the haematology laboratory tests at screening,
-
Serum creatinine less than1.5X ULN or calculated creatinine clearance greater than or equal to 50 mL/min
-
Albumin greater than 3 g/dL,
-
AST or ALT less than 2.5 × ULN (less than 5 × ULN if liver function abnormalities are due to hepatic metastasis).
-
Total serum bilirubin less than 1.5 × ULN (less than 3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation). 16. Ability to swallow study medication tablets and comply with study requirements.
17. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant, starting contraception at screening and continue throughout the study period and for 3 months after the final treatment administration, (during the treatment period and for at least 90 days after last dose of enzalutamide or at least 120 days after las dose of talazoparib, whichever occurs later) unless the patient is unable to maintain intercourse due to the androgen deprivation.
18. Subjects must not donate sperm starting at screening and throughout the study period and for 3 months after the final abiraterone acetate administration.
19. Subject agrees not to participate in another interventional study while with experimental medical products or anticancer drugs not approved in this setting on treatment in this study. Exceptions could be allowed for protocols investigating the survival or quality of life impact of common routine or conventional drugs (i.e. acetylsalicylic acid, statins, oral antidiabetic drugs) as long as they do not intefere with the study treatment and the evaluation of the main study arms.
20. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
-
Prior ARPi treatment for less than 12 weeks or disease progression (either PSA or radiographic progression) within 6 months of starting abiraterone or ARi.
-
Known or suspected brain metastasis or active leptomeningeal disease.
-
Symptomatic or impending spinal cord compression or cauda equina syndrome.
-
Use of opiate analgesia for pain from prostate cancer with average Brief pain inventory (BPI) questionnaire score higher than or equal to 6 and/or uncontrolled prostate cancer-related pain requiring increasing doses of opiates within 4 weeks prior to randomization
-
Prior treatment with more than one ARPi. This will include abiraterone, enzalutamide, apalutamide, or darolutamide, which are treatments with demonstrated PFS and/or OS benefit in mHPSC, as well as any other novel AR or androgen synthesis directed therapy (with the exception on LHRH/GnRH analogues and/or antagonists). Note: Patients who started on one ARPi and switched to another due to toxicity will only be eligible after prior discussion with the study chair, provided that they were on the first ARPi (other than enzalutamide) for a very limited period of time and can document that they were responding - without PSA rise or worsening symptoms - at the moment they were switched to the second ARPi. Inclusion of such cases will require written notification and approval from the study chair or co-chair.
-
Therapeutic radiation therapy within, 14 days (7 days for limited-field palliative radiotherapy) prior to study enrolment, or participants who have not recovered from radiotherapy-related toxicities to grade less than or equal to 1 according to NCI-CTCAE v.5.0.
-
Major surgery within 4 weeks prior to randomization or participants who have not recovered from the side effects of any major surgery.
-
Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study.
-
History of seizure or any condition that may predispose to seizure (i.e., prior significant brain trauma, brain vascular malformation, etc) or subjects that have had an unexplained loss of consciousness or transient ischemic attacks within 1 year previous to scheduled day 1 of treatment.
-
Congenital long QT syndrome or ECG at screening with QT interval corrected using Fridericia's formula (QTcF) greater than 500 milliseconds.
-
Participants with clinically significant cardiovascular disease including but not limited to any of the following:
- Stroke, transient ischemic attack, unstable angina pectoris or documented myocardial infarction within 12 months prior to study entry.
- Symptomatic pericarditis or clinically significant pericardial effusion or myocarditis
- Documented congestive heart failure (New York Heart Association Class, NYHA functional classification III-IV)
- Uncontrolled, persistent hypertension defined as systolic blood pressure greater than 170mmHg or diastolic blood pressure greater than100mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
-
Participants with any of the following cardiac conduction abnormalities:
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
- Conduction abnormality requiring a pacemaker.
- Other cardiac arrhythmia not controlled with medication.
-
Any clinically significant gastrointestinal disorder affecting absorption (i.e., extensive small bowel resection, active inflammatory bowel disease).
-
Active or symptomatic viral hepatitis or chronic liver disease.
-
Known/possible hypersensitivity, allergies to enzalutamide, talazoparib or any of capsule excipients.
-
Other malignancy except:
- Carcinoma in situ or non-melanoma skin cancer.
- A cancer diagnosed and treated greater than or equal to 5 years before randomization with no subsequent evidence of recurrence.
-
Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Control
Enzalutamide 160 mg orally daily continuously in 28-day cycles. |
Enzalutamide capsules 160 mg orally daily |
|
실험적: Enzalutamide and Talazoparib. Post-AA/ARi according to prior treatment.
Enzalutamide 160 mg and Talazoparib 0.5 mg both orally daily and continuously in 28-day cycles. Note: Patients who previously received Enzalutamide will be included directly into the investigational arm. (Up to a maximum of 6). |
Enzalutamide capsules 160 mg plus talazoparib capsules 0.5 mg, both orally daily |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
PSA response (PSA50)
기간: within the first 16 weeks
|
Percentage of participants with a PSA decline greater than or equal to 50 percent from baseline confirmed by a consecutive PSA value (taken at least 3 weeks apart), prior to PSA progression |
within the first 16 weeks
|
|
Objective response rate (ORR)
기간: during the first 16 weeks
|
Defined as the best overall radiographic response (partial or complete) during the first 16 weeks on follow up as per investigator assessment of soft tissue/visceral disease per RECIST 1.1 in subjects who have a measurable tumour and/or Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases |
during the first 16 weeks
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Radiographic Progression Free Survival (rPFS)
기간: Through study completion, an average of 2 years
|
Time from randomization to first objective evidence of radiographic progression, based on RECIST 1.1 for soft tissue/visceral disease and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines for bone metastases, or death, whichever occurs first. |
Through study completion, an average of 2 years
|
|
Time to PSA Progression (TTPP)
기간: Through study completion, an average of 2 years
|
Time from randomization to PSA progression defined as PSA greater than or equal to 25 percent and greater than or equal to 2ng/mL from nadir (or baseline for participants with no PSA decline), confirmed by a second value obtained 3 or more weeks apart as per PCWG3 guidelines. |
Through study completion, an average of 2 years
|
|
Time to unequivocal clinical progression (TTCP)
기간: Through study completion, an average of 2 years
|
Time from randomization to clinical worsening of prostate cancer related symptoms, as new onset cancer pain requiring chronic administration of opiate analgesia, deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to 3 or higher, time to first skeletal-related event (the time from randomization to first incidence of radiotherapy to the bone or bone surgery, pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain); or initiation of subsequent lines of active treatment including cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications or symptoms related to disease progression. |
Through study completion, an average of 2 years
|
|
Progression Free Survival (PFS)
기간: Through study completion, an average of 2 years
|
Time from randomization to PSA progression, unequivocal clinical progression or radiographic progression, whichever occurs first. |
Through study completion, an average of 2 years
|
|
Incidence of adverse events (AEs)
기간: Through study completion, an average of 2 years
|
Total, grouped by grades and AEs category, related and unrelated with the trial treatment. The AEs Defined as incidence of prespecified AEs as per National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, change from baseline in targeted vital signs and change from baseline in targeted clinical laboratory test results. |
Through study completion, an average of 2 years
|
|
Incidence of serious adverse events (SAEs)
기간: Through study completion, an average of 2 years
|
Number of Serious Adverse Events, related and unrelated. SAEs leading to treatment discontinuation. |
Through study completion, an average of 2 years
|
|
Drug compliance
기간: Through study completion, an average of 2 years
|
Percentage of dose taken for each treatment drug, dose reductions, dose discontinuation (temporary or permanent) |
Through study completion, an average of 2 years
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Assessment of PSA response rate
기간: Through study completion, an average of 2 years
|
In participants with and without germline and/or somatic DDR alterations. |
Through study completion, an average of 2 years
|
|
Assessment of ORR
기간: Through study completion, an average of 2 years
|
In participants with and without germline and/or somatic DDR alterations |
Through study completion, an average of 2 years
|
|
Assessment of rPFS
기간: Through study completion, an average of 2 years
|
In participants with and without germline and/or somatic DDR alterations |
Through study completion, an average of 2 years
|
|
Assessment of TTPP
기간: Through study completion, an average of 2 years
|
In participants with and without germline and/or somatic DDR alterations. |
Through study completion, an average of 2 years
|
|
Assessment of TTCP
기간: Through study completion, an average of 2 years
|
In participants with and without germline and/or somatic DDR alterations. |
Through study completion, an average of 2 years
|
|
Changes in expression levels of AR in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Changes in expression levels of AR in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Changes in expression of AR-related genes in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Changes in expression of AR-related genes in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Changes in open chromatin regions in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Changes in open chromatin regions in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Survival signaling in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Survival signaling in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
DNA-damage in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
DNA-damage in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Deficient/proficient DNA-repair in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Deficient/proficient DNA-repair in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Other biomarkers in tissue
기간: Through study completion, an average of 2 years
|
Changes from tissue samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
|
Other biomarkers in plasma
기간: Through study completion, an average of 2 years
|
Changes from plasma samples, studying the correlation of these changes with clinical activity |
Through study completion, an average of 2 years
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Elena Castro, Dra., Hospital 12 de Octubre
- 연구 의자: David Olmos, Dr., Hospital 12 de Octubre
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- TEAM PC_FOS06/2023
- 2023-510536-37-00 (씨티스)
- 2023 (미국 NIH 보조금/계약)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .