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

talazoparib plus enzalutamide

Placebo plus enzalutamide

Pfizer CT.gov Call Center

The purpose of the study is to evaluate the safety and efficacy of talazoparib in combination with enzalutamide compared with placebo in combination with enzalutamide in participants with DDR-deficient mCSPC.

The study will have 5 periods: prescreening, screening, double-blind treatment, safety follow-up, and long-term follow-up.

Approximately 550 men with mCSPC will be randomized. Eligible participants will be randomly assigned to either of 2 treatment groups as follows:

* Talazoparib in combination with enzalutamide.
* Placebo capsules identical in appearance to talazoparib capsules in combination with enzalutamide.

Talazoparib or identical placebo treatment will be blinded. Enzalutamide (160 mg/day) will be open label. The dose of talazoparib/placebo to be given in combination with enzalutamide is 0.5 mg once daily. Participants with moderate renal impairment (eGFR 30-59 mL/min/1.73 m2 by the MDRD equation) at screening may be enrolled and the talazoparib/placebo dose will be 0.35 mg once daily.

Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC

TALAPRO-3: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, STUDY OF TALAZOPARIB WITH ENZALUTAMIDE VERSUS PLACEBO WITH ENZALUTAMIDE IN MEN WITH DDR GENE MUTATED METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first

time from randomization to death from any cause

proportion of patients with measurable soft tissue disease at baseline with objective response per RECIST 1.1

duration of responses in patients with measurable soft tissue disease at baseline per RECIST 1.1

proportion of patients with PSA response grater than or equal to 50%

Time from randomization to initiation of antineoplastic therapy

time from randomization to first symptomatic skeletal event (symptomatic fractures, spinal cord compression, surgery or radiation to the bone whichever is first)

time from randomization to opiate use for prostate cancer pain

AEs and SAEs incidence by type and severity (graded by NCI CTCAE version 4.03)

plasma concentrations of enzalutamide and its metabolite

change from baseline in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)

time to deterioration in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)

change from baseline in participant-reported general health status per EQ-5D-5L

change from baseline in patient-reported Global health status/QoL per EORTC QLQ-C30

time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30

time to definitive deterioration in disease specific urinary symptoms per EORTC QLQ-PR25

Astellas Pharma Inc

Pfizer

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Disease Progression

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Niraparib

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Niraparib 200mg PO daily on days 1-28 of each 28-day cycle. Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Nivolumab

Niraparib 200mg PO daily on days 1-21 of each 21-day cycle. Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

Niraparib + Ipilimumab

The main purpose of this study is to look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.

Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy

PARPVAX: Parpvax: A Phase 1b/2, Open Label Study of Niraparib Plus Either Ipilimumab or Nivolumab in Patients With Advanced Pancreatic Cancer Whose Disease Has Not Progressed on Platinum-based Therapy

The PFS6 rate will be estimated using the Kaplan-Meier method, and the 95% confidence interval will be estimated from the Kaplan-Meier curve. The null hypothesis is that the PFS6 rate in this population of subjects is 44%.

Progressive disease is defined as at least a 20% increase in the sum of all the longest diameter (LD) of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions is also considered progression.

Target lesions assessed according to RECIST v1.1.

The incidence of adverse events (AEs), clinical laboratory abnormalities and dose modifications.

Identification of HRDs and allele specific LOH via whole exome sequencing

Assessed using immune biomarkers, and RNAseq of PBMC

Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)

start of treatment to death due to any cause or last patient contact alive

Bristol-Myers Squibb

GlaxoSmithKline

University of Pennsylvania

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Nivolumab (Arm A)

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

Niraparib + Ipilimumab (Arm B)

Niraparib + Nivolumab

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Arm A

Niraparib + Ipilimumab

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

Arm B

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Regulatory Lead

The efficacy population will consist of all patients who received at least one dose of study treatment and had a least one post-treatment assessment of response by RECIST v.1.1.

Rate of Progression-free Survival at 6 Months (PFS6)

Safety and Tolerability of This Combination as Determined by CTCAE v5.0.

Proportion of Tumors With Homologous Recombination Deficits (HRD), in Patients With Stability or Response to Platinum Therapy

Correlation of HRDs With Response to Treatment With Niraparib Plus Immune Checkpoint Blockade

Immune Activation Prior to Treatment

Immune Activation During Treatment

Overall Response Rate

Duration of Response (DOR)

Overall Survival (OS)

Overall Study

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Cisplatin

The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab. Tumor biopsies will be performed at baseline, after the second cycle and at progression with appropriate written informed consent and the samples will be analyzed. Biomarker research will be performed.

The patients will receive intravenously nivolumab at dose of 240 mg every 2 weeks (240mg q2w). The patients will undergo tumor biopsy at baseline and within 24-72h after the second administration of treatment, and at progression of their disease.

The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab 240mg IV q 2 weeks. Patient samples will be collected with appropriate written informed consent and analyzed.

Biomarker Research

The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab 240mg IV q 2 weeks.

AMANDA PSYRRI, MD

ELENI PAPASTAMATIOU

Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

HNSCC whose disease has progressed within 6 months after platinum-based chemotherapy. The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities and guide combination strategies.

Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and Neck Squamous Carcinoma (HNSCC) whose disease has progressed within 6 months after platinum-based chemotherapy. The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities and guide combination strategies. The greatest focus has been on tumor-cell programmed death Ligand 1 (PD-L1) expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. PD-L1 expression can be transient, and intrapatient and even intratumor heterogeneity in PD- L1 tumor expression can exist. Therefore, tumor sampling at one timepoint might not accurately reflect the state of PD1 axis in a patient. Another important aspect is that PD-L1 immunohistochemistry alone does not take into account factors that could impede the anti-PD1 therapy response such as whether or not active immune cell engagement of the PD1 axis occurs in the tumor microenvironment or other concurrent immune suppressive pathways are present.

Assessment of biomarkers at baseline may not predict benefit from immunotherapy. In a phase II study of ipilimumab in patients with metastatic melanoma baseline tumor infiltrating lymphocyte status was not associated with clinical activity. However, increase in tumor infiltrating lymphocyte density in tumor biopsy samples collected after the second dose of ipilimumab was associated with significantly greater clinical activity with ipilimumab compared to samples without increase in lymphocyte density. For a better understanding of the mechanisms of resistance to nivolumab in HNSCC, the investigators propose to study a cohort of longitudinal HNSCC samples from recurrent/metastatic HNSCC patients treated with nivolumab and identify biomarkers of response and resistance. The investigators will specifically focus on modulation of immune phenotype (ImmR) following two cycles of nivolumab as surrogate biomarker for response to nivolumab.

The primary endpoint will be the change in the percentage of immune cells that is caused by nivolumab treatment. Secondary endpoint will be safety of performing a biopsy after second nivolumab dose. Translational correlates will be tested in tumour tissue, plasma and germline DNA.

Investigator assessment of best overall response (BOR), determined between the date of first dose and the last tumor assessment (TA), will be image-based and scored using the RECIST 1.1. criteria. BOR will be defined as categorical variable with 3 levels { Benefit (complete response (CR), partial response (PR), stable disease (SD) lasting 6 months from the first nivolumab dose), no benefit (PD, progressive disease or SD lasting less than 6 months from the first nivolumab dose), and unknown} Longitudinal tissue biopsies will be collected from HNSCC patients treated with nivolumab . Biopsies will be taken at baseline, 24-72 hours after the second cycle of nivolumab and at progression.

Longitudinal tissue biopsies will be collected from HNSCC patients treated with nivolumab Biopsies will be taken at baseline, 24-72 hours after the second cycle of nivolumab and at progression.

Predictive Biomarkers for Response to Nivolumab in Head and Neck Squamous Cell Carcinoma

Predictive Biomarkers For Response To Nivolumab In Head and Neck Squamous Cell Carcinoma

Primary endpoint will be the change in mean percentage of immune cells that is caused by the nivolumab treatment

Incidence of adverse events attributable to nivolumab treatment

BOR will be defined as categorical variable with 3 levels { Benefit (complete response (CR), partial response (PR), stable disease (SD) lasting 6 months from the first nivolumab dose), no benefit (PD, progressive disease or SD lasting less than 6 months from the first nivolumab dose), and unknown}

NCI common toxicity criteria will be used

Targeted gene sequencing using next generation sequencing will be performed

Nanostring gene expression profiling, multiple tumor, inflammatory- and immune related genes will be analyzed by multiplex Nanostring technology by using the nCounter PanCancer Immune Profiling 770-plex gene expression Panel

PD-L1 will be assessed in tumor cells and immune cells by immunohistochemistry

It will be assessed at RNA and protein level

The assessment will be performed using multiplex imaging

PD-L2 will be assessed in tumor cells and immune cells by immunohistochemistry

The assessment will be performed with Parsotrix system

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC	NCT04821622	Prostate Cancer	talazoparib plu... Placebo plus en...	18 Years -	Pfizer
Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy	NCT03404960	Pancreatic Aden...	Niraparib + Niv... Niraparib + Ipi...	18 Years -	University of Pennsylvania
Predictive Biomarkers for Response to Nivolumab in Head and Neck Squamous Cell Carcinoma	NCT03652142	HNSCC DNA Damage DNA Double Stra...	Biomarker Resea... Nivolumab	18 Years -	Attikon Hospital
Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC	NCT04821622	Prostate Cancer	talazoparib plu... Placebo plus en...	18 Years -	Pfizer

Spots Global Cancer Trial Database for ddr

Every month we try and update this database with for ddr cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for ddr

Every month we try and update this database with for ddr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ddr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.