Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

ZEN003694 will be administered PO QD with Talazoparib PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD as monotherapy at the RP2D in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 PO QD with Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

ZEN003694

This is a two-part open label, non-randomized, Phase 2, study of ZEN003694 in combination with Talazoparib in patients with TNBC without germline mutations of BRCA1 or BRCA2. Part 1 is a dose escalation and Part 2 is a Simon 2-Stage design. There are 3 expansion cohorts: Expansion Cohort A (combination treatment in post-TROP2-ADC patients), Expansion Cohort B (ZEN003694 monotherapy), and Expansion Cohort C (combination treatment in TROP2-ADC-naive patients).

A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer

A Phase 2b Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer

Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably or definitely related to study drug.

CBR defined as a confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST v1.1

ORR defined as a confirmed complete response (CR) or partial response (PR) by RECIST 1.1

CBR defined as a confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST 1.1

Time from randomization to documented disease progression or death

For subjects with a confirmed response of PR or CR, duration of response is measured from the date of the first response until the time that overall disease progression (radiographic progressive disease or clinical deterioration) or death is documented.

Plasma concentrations of ZEN003694 and the active metabolite ZEN003791 will be measured.

Plasma concentrations of talazoparib will be measured.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much), higher scores=high level of symptom/problems.

Pfizer

Newsoara Biopharma Co., Ltd.

Zenith Epigenetics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.

This is an open label, Phase 1, dose escalation and dose confirmation study of ZEN003694 in patients with mCRPC.

A Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase 1 Safety and Tolerability Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer

A DLT is a treatment-related, clinically significant adverse event or laboratory abnormality occurring during the first cycle of treatment (Day 1 thru Day 28).

AUC is defined as the area under the curve (plasma concentration of drug over time).

Cmax is defined as maximum or peak plasma concentration of drug.

Cmin is defined as minimum or trough plasma concentration of drug.

Tmax is defined as the time from dosing to the maximum plasma concentration.

t/12 is defined as the half-life of drug.

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Rare Diseases

Lymphoma

Sarcoma

Brain Neoplasms

Medulloblastoma

Neuroblastoma

Lymphosarcoma

Soft Tissue Sarcoma

* Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles.
* Patients with unselected relapsed or refractory solid tumors or lymphoma

* Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles.
* Patients with relapsed or refractory solid tumors or lymphoma that have defined molecular features predicted to increase sensitivity to BET inhibition

* Patients will receive BMS-986378 (also known as CC-90010) monotherapy orally for 4 days every 28 days.
* Patients with relapsed or refractory CNS tumors or CNS metastatic tumors

* Patients will receive BMS-986378 (also known as CC-90010) monotherapy orally for 4 days every 28 days.
* Patients with relapsed or refractory CNS tumors or CNS metastatic tumors that have defined molecular features predicted to increase sensitivity to BET inhibition

BMS-986158 belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

BMS-986158

BMS-986378 (also known as CC-90010) belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

BMS-986378

Steven G. DuBois, MD, MS

Arm 1 of this research study is studying an investigational drug called BMS-986158 as a possible treatment for pediatric solid tumors or lymphoma. Arm 2 of this research study is studying an investigational drug called BMS-986378 (also known as CC-90010) as a possible treatment for pediatric brain tumors or pediatric tumors that have spread to the brain.

This is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved BMS-986158 or BMS-986378 as a treatment for any disease.

BMS-986158 and BMS-986378 are currently still being studied in adults. This is the first time that BMS-986158 or BMS-986378 will be evaluated in younger children, though children 12-17 years of age may also be included in parts of adult studies of BMS-986158.

Research in the laboratory has shown that BMS-986158 and BMS-986378 may have activity against cancer cells. These drugs belong to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer

Phase 1 Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 (CC-90010) in Pediatric Cancer

Dose limiting toxicity as defined in protocol

Adverse events coded using CTCAE version 5

Plasma concentrations of BMS-986158 or BMS-986378

Gene expression levels in peripheral blood

Stand Up To Cancer

Dana-Farber Cancer Institute

Principal Investigator

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.

Enzalutamide

Zenith Study Team

This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry.

The patient population will be separated into two cohorts:

Cohort A: Patients with poor response to prior abiraterone defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: \< 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone

Cohort B: Patients with response to prior abiraterone, defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and confirmed PSA50 response

ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer

A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.

Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3

Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment.

Time from date of randomization to the date of death from any cause

PSA response is a reduction in serum PSA concentration of ≥50% from baseline.

Proportion of the patients who have either a complete response (CR) or partial response (PR) by RECIST 1.1 criteria who have measurable disease at baseline.

EORTC QLQ-C30: cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

EORTC QLQ-PR25: prostate cancer specific instrument with 25 questions used in conjunction with EORTC QLQ-C30 to assess the participant QoL. Used to evaluate 5 multi-item scales (urinary, bowel, and hormonal treatment-related symptoms, sexual activity, and sexual functioning) and one single item (problems due to incontinence aid use). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

Time from date of randomization to the first dose of chemotherapy.

Time from date of randomization to the first SRE such as pathological fracture, surgery/radiotherapy for pain/prevention of fracture, hypercalcemia, and spinal cord compression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer	NCT03901469	Triple Negative...	ZEN003694 Talazoparib	18 Years -	Zenith Epigenetics
A Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer	NCT02705469	Metastatic Cast...	ZEN003694	18 Years -	Zenith Epigenetics
Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer	NCT03936465	Solid Tumor, Ch... Lymphoma Brain Tumor, Pe...	BMS-986158 BMS-986378	1 Year - 21 Years	Dana-Farber Cancer Institute
ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer	NCT04986423	Metastatic Cast...	ZEN003694 Enzalutamide	18 Years -	Zenith Epigenetics
A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer	NCT03901469	Triple Negative...	ZEN003694 Talazoparib	18 Years -	Zenith Epigenetics
ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer	NCT04986423	Metastatic Cast...	ZEN003694 Enzalutamide	18 Years -	Zenith Epigenetics

Spots Global Cancer Trial Database for bromodomain

Every month we try and update this database with for bromodomain 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.

Spots Global Cancer Trial Database for bromodomain

Every month we try and update this database with for bromodomain 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 bromodomain 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.