Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients will receive enzalutamide capsules orally once daily continuously (160 mg) in addition to standard ADT (unless surgical castration).

Patients will receive enzalutamide capsules 160 mg in combination with talazoparib (PF-06944076) capsules 0.5 mg, both orally daily and continuously in 28-day cycle, in addition to standard ADT (unless surgical castration).

Enzalutamide capsules orally once daily and continuously (160 mg) in 28-day cycles (every four weeks)

Enzalutamide

Talazoparib capsules orally once daily and continuously (0.5 mg) in 28-day cycles (every four weeks)

Joaquin Mateo

This is a multicenter, open-label, randomized, two-arm, phase II clinical trial to evaluate the efficacy and safety of talazoparib (PF-06944076) in combination with enzalutamide in patients with metastatic hormone-naïve prostate cancer (mHNPC)

Men age ≥ 18 years with high-volume mHNPC that are not candidates for curative intent and have not received previous systemic treatment with any other agent for unresectable locally advanced or mHNPC.

After signing ICF and confirm eligibility, patients will start treatment with enzalutamide in addition to standard ADT. After 2 cycles of enzalutamide-containing regimen, patients will be randomized in a 1:2 ratio to:

Cohort A - Enzalutamide 160 mg orally daily continuously; Cohort B - Enzalutamide 160 mg in combination with talazoparib (PF-06944076) 0.5 mg, both orally daily and continuously in 28-day cycles.

In either arm, patients will be requested to continue ADT throughout trial participation (unless surgical castration).

Randomization will be stratified based on HR gene alterations (presence versus absence/unknown) detected in the baseline biopsy.

Patients will receive treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and at least the first two new anti-cancer therapies will be collected every six months (± 14 days) from the last dose of investigational product until the end of study (EoS).

Enzalutamide Plus Talazoparib for the Treatment of Hormone Sensitive Prostate Cancer (ZZ-First)

A Randomized Phase II Trial to Evaluate the Antitumor Activity of Enzalutamide and Talazoparib (PF-06944076) for the Treatment of Metastatic Hormone-naïve Prostate Cancer

The primary efficacy endpoint for the study is the PSA-CR. The PSA-CR is defined as the percentage of patients with PSA \< 0.2 ng/mL divided by the number of patients in the analysis set.

PSA-CR is defined as the number of patients with PSA \<0.2 ng/mL from randomization to Cycle 7 Day 1 therapy divided by the number of patients in the analysis set.

PSA response is defined as the number of patients with PSA \<0.4 ng/mL from randomization to 7- or 12-months therapy divided by the number of patients in the analysis set

TCP is defined as the time from randomization to clinical progression, based on progression in bone as per 2+2 rule, progression per RECIST criteria v1.1. or clinical deterioration due to cancer per investigator's opinion.

PSA-PD in accordance with PCWG3 criteria, is defined as the time from randomization to PSA progression.

PSA-PFS in accordance with based on Prostate Cancer Working Group 3 (PCWG3) criteria (PSA ≥ 25% and ≥ 2 ng/mL from nadir confirmed by a second value obtained 3 or more weeks later).

PFS is defined as the time from randomization to radiological progression based on progression in bone as per 2+2 rule or progression per RECIST criteria v1.1.

TTCR prostate cancer is defined as the time from randomization to PSA progression in accordance with PCWG3 criteria or clinical progression, whichever occurred first.

OS is defined as the time from randomizatiom date to date of death due to any cause or the last date the patient was known to be alive.

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.

Pfizer

MedSIR

Docetaxel

Tubulin Modulators

Antimitotic Agents

Hormone Antagonists

Radiation therapy combined with weekly docetaxel (20 mg/m2) and hormone therapy.

Hormone and radiation therapy

Radiation therapy

A prospective, multicenter, parallel-group, open-label, randomized, phase II Clinical Study of Radiation Therapy, Hormone Therapy and Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients with High-Risk Localized Prostate Cancer (Stage III and IV) whose primary objective is determine the percentage of patients free of biochemical recurrence within 5 years of receiving a combination of radiation therapy with docetaxel associated with hormone therapy or the standard of care of radiation therapy and hormone therapy in patients with stage III and IV localized prostate cancer with a poor prognosis.

Randomized Phase II Clinical Study of Radiation Therapy, Hormone Therapy and Chemotherapy with Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients with High-Risk Localized Prostate Cancer (Stage III and IV) Primary Objective: To determine the percentage of patients free of biochemical recurrence within 5 years of receiving a combination of radiation therapy with docetaxel associated with hormone therapy or the standard of care of radiation therapy and hormone therapy in patients with stage III and IV localized prostate cancer with a poor prognosis.

Design: A prospective, multicenter, multidisciplinary, parallel-group, open-label study with randomized group assignment.

A prospective, multicenter, multidisciplinary, parallel-group, open-label study with randomized group assignment

Radiation-hormone and Docetaxel VS Radiation-hormone in Patients With High-Risk Localized Prostate Cancer

Randomized Phase II Clinical Study of Radiation Therapy, Hormone Therapy and Chemotherapy With Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients With High-Risk Localized Prostate Cancer (Stage III and IV)"

Percentage of patients free of elevation of PSA by 2 ng/mL above the minimum level reached since treatment (biochemical reccurrence), calculating the at-call event, i.e., the date of last confirmatory test (Phoenix criteria).

The duration of survival, in months, between randomization of the patient in the study and the date of recurrence by PSA. In the remaining patients, the last available follow-up will be taken as the last control

The duration of survival, in months, between randomization of the patient in the study and the date of recurrence by PSA, clinical manifestations or death due to disease. In the remaining patients, the last available follow-up will be taken as the last control

Defined as the time that elapses, in months, between randomization of the patient in the study and the date of death, regardless of the cause. In the remaining patients, the last available follow-up will be taken as the last control.

The clinical response rate: percentage of patients with partial and complete response, according to RECIST criteria.

Biochemical response rate: percentage of patients with partial and complete response, according to PSA levels.

Change from baseline in the Quality of Life Questionnaire C30 scale (QLQ-C30) to week 9. The QLQ-c30 has five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. They are assigned values between 1 and 4 (1: nothing, 2: a few, 3: enough, 4: a lot) according to the patient's responses to the item, only in items 29 and 30 are assessed with a score from 1 to 7 (1: terrible, 7: excellent). The obtained scores are summed and standardized and gets a score between 0 and 100

Numbers of events evaluated according to NCI criteria CTCAE v3

Pivotal S.L.

Spanish Oncology Genito-Urinary Group

Nivolumab

Immunomodulating Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Stereotactic body radiotherapy of 8 Gray (Gy) x 3 on one soft tissue or bone metastasis + Nivolumab 3mg/kg IV every 3 weeks (Q3W) + Ipilimumab 1mg/kg IV Q3W for four doses, then Nivolumab 480 mg IV every 4 weeks (Q4W) for up to 52 weeks treatment in total

Nivolumab 3mg/kg IV Q3W + Ipilimumab 1mg/kg IV Q3W for four doses, then Nivolumab 480 mg IV Q4W for up to 52 weeks treatment in total

Stereotactic body radiotherapy

Ipilimumab Injection [Yervoy]

Nivolumab 3mg/kg IV Q3W for four doses, then then Nivolumab 480mg IV Q4W

Nivolumab Injection [Opdivo]

Biopsies

Rikke HL Eefsen, MD, PhD

Nicklas J Spindler, MD

The goal of this investigator-initiated, single-center, and randomized phase II trial is to investigate the potential synergistic effect of combining stereotactic body radiotherapy of a single soft tissue- or bone metastasis with ipilimumab and nivolumab in patients with mCRPC and perform translational analyses on tissue and blood, searching for predictive biomarkers of efficacy and toxicity.

Participants will be randomized to receive ipilimumab and nivolumab with or without stereotactic body radiotherapy (SBRT).

The participants receive treatment for 52 weeks, including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.

Biopsies from metastatic sites are collected at baseline, before the third treatment, and at the end of treatment. Blood sampling for immune monitoring and circulating tumor DNA is performed consecutively at baseline and every radiographic assessment.

Checkpoint Inhibitors and SBRT for mCRPC

Randomised Phase 2 Trial of Stereotactic Body Radiation Therapy, SBRT in Combination With Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer

According to International Committee of Medical Journal Editors (ICMJE) guideline:

Will individual participant data be available (including data dictionaries)? No.

What data in particular will be shared? None.

What other documents will be available? Study Protocol, Statistical Analysis Plan, analytic software code.

When will data be available (start and end dates)? The study protocol is available from the beginning of the trial. Statistical analysis plan and analytic code will be available beginning 3 months and ending 5 years following the article publication of the primary endpoint.

With whom? Investigators who state their purpose.

For what types of analyses? Any

By what mechanism will data be made available? Proposals should be directed to the PI.

Objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumours (RECIST1.1) per Prostate Cancer Clinical Trials Working Group (PCWG3) criteria for patients with measurable disease

Prostate-specific antigen (PSA) response rate of ≥ 50% decline from baseline at any time from treatment start (confirmed after ≥ 4 weeks, all patients with measurable and non-measurable disease)

Common Terminology Criteria for Adverse Events (CTCAE) v. 5

Per PCWG3 with 2+2 rule and clinical progression (all patients)

Per RECIST 1.1 and Immune Response Evaluation Criteria in Solid Tumours (iRECIST)

Questionaire The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of cancer patients. It includes 30 questions, divided into three major dimensions of global health status, functional-, and symptoms scale. The scales are calculated into a score ranging from 0-100. A high score on global health status and functional scales represents a better quality of life, but a high score on the symptoms scale represents a high burden of symptoms/low quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Enzalutamide Plus Talazoparib for the Treatment of Hormone Sensitive Prostate Cancer (ZZ-First)	NCT04332744	Metastatic Pros...	Enzalutamide Talazoparib	18 Years -	MedSIR
Radiation-hormone and Docetaxel VS Radiation-hormone in Patients With High-Risk Localized Prostate Cancer	NCT03432780	Prostate Cancer... Prostate Cancer...	Docetaxel Hormone and rad... Radiation thera...	18 Years -	Spanish Oncology Genito-Urinary Group
Enzalutamide Plus Talazoparib for the Treatment of Hormone Sensitive Prostate Cancer (ZZ-First)	NCT04332744	Metastatic Pros...	Enzalutamide Talazoparib	18 Years -	MedSIR
Radiation-hormone and Docetaxel VS Radiation-hormone in Patients With High-Risk Localized Prostate Cancer	NCT03432780	Prostate Cancer... Prostate Cancer...	Docetaxel Hormone and rad... Radiation thera...	18 Years -	Spanish Oncology Genito-Urinary Group
Checkpoint Inhibitors and SBRT for mCRPC	NCT05655715	Prostate Cancer... Castrate Resist... Metastatic Cast... Prostate Cancer...	Stereotactic bo... Ipilimumab Inje... Nivolumab Injec... Biopsies	18 Years -	Herlev and Gentofte Hospital

Spots Global Cancer Trial Database for prostate cancer stage iv