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All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Arm 1 will enroll patients with either AML or MDS

Arm 2 will enroll patients with either CLL or MCL

Oral capsule with multiple dosage forms given once daily

BMN 673

Pfizer CT.gov Call Center

This is a two-arm, open-label study to determine the maximum tolerated dose (MTD) and assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMN 673 in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Arm 1 will enroll patients with either AML or MDS; Arm 2 will enroll patients with either CLL or MCL.

Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies

Phase 1, Two-arm, Open-label Study Of Once Daily, Oral Bmn 673 In Patients With Advanced Hematological Malignancies

Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Sample collection times vary per visit. PK parameters that will be evaluated include: maximum concentration (Cmax), minimum concentration (Cmin), time to maximum plasma concentration (Tmax), area under the curve from 0 to last quantifiable sampling point postdose (AUC0-inf), area under the curve extrapolated to infinity (AUC0-last), half life (t1/2), systemic clearance (CL/f) and volume of ditribution (VZ/f)

Medivation, Inc.

Pfizer

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Poly (ADP-ribose) polymerase (PARP) inhibitor; has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.

Alice P Chen, M.D.

Background:

* The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of deoxyribonucleic acid (DNA) damage repair mechanisms.
* Talazoparib (BMN 673) is a PARP inhibitor with greater in vitro activity than any other PARP inhibitor currently in development. BMN 673 has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines and has potent antitumor activity in animal models of tumors harboring mutations in DNA repair pathways.
* BMN 673 is showing promising single-agent activity in patients with advanced ovarian and breast cancer harboring deleterious BRCA mutations.
* This pilot study will evaluate the pharmacodynamic effects of BMN 673 on DNA damage and apoptosis markers in tumor biopsy tissue.

Primary Objective:

-Determine the pharmacodynamic effect of BMN 673 in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations.

Secondary Objectives:

* Determine the response rate (Complete Response (CR) + Partial Response (PR) of treatment with BMN 673 in patients with advanced ovarian or primary peritoneal carcinoma and deleterious BRCA mutations.
* Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced breast carcinoma and deleterious BRCA mutations.
* Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced solid tumor (other than breast or ovarian) and deleterious BRCA mutations.

Eligibility:

* Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options.
* No major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels.
* Age greater than or equal to 18 years of age; Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 2
* Adequate organ function.
* Willingness to undergo tumor biopsies.

Study Design:

* BMN 673 will be administered orally each day in 28-day cycles.
* Dosing will be at the established recommended Phase II dose of 1000 mcg/day each day for

  28 days.
* We plan to accrue a total of 12 evaluable patients per cohort for a total of 36 patients. To allow for some patients who will not be evaluable, the accrual ceiling is 42 patients.
* Tumor biopsies will be mandatory at baseline (pre-dose), and then approximately 3-6 hours post BMN 673 on day 8. An optional tumor biopsy may also be collected at time of disease progression.

SCHEMA

* BMN 673 is administered orally each day in 28-day cycles
* Tumor biopsies will be performed at baseline (pre-treatment) and 3-6 hrs post dose on cycle 1 day 8. An optional tumor biopsy may also be collected at time of disease progression. Tumor biopsies will be evaluated for protease activated receptor (PAR) levels, DNA damage response markers such as \>=H2A.X Variant Histone (H2AX), cleaved caspase 3, excision repair cross-complementing group 1 (ERCC1), pNbs1, XPF, RAD51, and pT1989ATR, and, as indicators of ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM) activation, Checkpoint kinase 1 (chk1) and Checkpoint kinase 2 (chk2)
* Blood samples for circulating tumor cells (CTC) analyses will be collected at baseline (pre-treatment), on cycle 1 day 1(3-6 hours post dose), on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 (3-6 hours post dose)
* Blood samples for pharmacokinetic (PK) analysis will be collected on cycle 1 day 1 pre-dose and 0.5, 1, 2, 3, 4, 6,8, and 24 hours post-dose, on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 pre-dose and 3-6 hours post dose.

Background:

* The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of deoxyribonucleic acid (DNA) damage repair mechanisms.
* Talazoparib (BMN 673) is a PARP inhibitor with greater in vitro activity than any other PARP inhibitor currently in development. Talazoparib (BMN 673) has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in DNA repair pathways.
* Talazoparib (BMN 673) is showing promising single-agent activity in patients with advanced ovarian and breast cancer harboring deleterious BRCA mutations.
* This pilot study will evaluate the pharmacodynamic effects of talazoparib (BMN 673) on DNA damage and apoptosis markers in tumor biopsy tissue.

Primary Objective:

-Determine the pharmacodynamic effect of talazoparib (BMN 673) in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations.

Secondary Objectives:

-Determine the response rate (Complete Response (CR) + Partial Response (PR) of treatment with talazoparib (BMN 673) in patients with deleterious BRCA mutations.

Eligibility:

* Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options.
* No major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels.
* Age greater than or equal to 18 years of age; Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 2
* Adequate organ function.
* Willingness to undergo tumor biopsies.

Study Design:

* Talazoparib (BMN 673) will be administered orally each day in 28-day cycles.
* Dosing will be at the established recommended Phase II dose of 1000 microgram/day each day for 28 days.
* To meet the primary, pharmacodynamic endpoint of the trial, we plan to accrue a total of 12 patients with matched, evaluable baseline and day 8 biopsies. To allow for some patients whose biopsies will not be evaluable (i.e., will contain \<5% tumor content), the accrual ceiling is 24 patients. The number of patients evaluable for objective response, while relevant to the secondary objective of the trial, will not be considered in determining completion of accrual.
* Tumor biopsies will be mandatory at baseline (pre-dose), and then approximately 3-6 hours post talazoparib (BMN 673) on day 8. One optional tumor biopsy may also be collected either on day 1 (+/- 2 days) of the cycle following any restaging at which a 10-19% increase in tumor volume is observed (according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria) if the patient has been on study for at least 4 cycles, or at time of disease progression.

Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Evaluation of drug effect on deoxyribonuclecic acid (DNA) damage response will be performed using immunofluorescence assays to measure the DNA damage repair marker γH2A (the phosphorylated form of histone family member X, H2AX) in the nucleus of tumor cells obtained via core biopsy.

Response will be evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)1. 1 guidelines; restaging scans will be carried out every 2 cycles. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. And progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

National Cancer Institute (NCI)

Principal Investigator

Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.

Talazoparib (BMN 673)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Alice P. Chen

Percent of Participants Who Achieve a Sustained Progressive Disease (PD) Response, Defined to be at Least 4% Nuclear Area Positive (NAP) γH2AX at the Day 8 Biopsy

Complete Response

Partial Response

Response Rate (Complete Response (CR) + Partial Response (PR) of Treatment With Talazoparib (BMN 673) in Participants With Deleterious Breast Cancer (BRCA) Mutations

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

BMN 673 daily until progression, death, unacceptable toxicity, withdrawal of consent or any other criterion felt by the Investigator to preclude continuation of treatment.

Starting oral dose of 1.0 mg once daily to be taken until progression, death, unacceptable toxicity, withdrawal consent or any other criterion felt by the Investigator to preclude continuation of treatment.

Rebecca Kristeleit

A Single Arm Phase II Trial of BMN 673 for Inoperable, Advanced Endometrial Cancer With Retrospective PTEN, MSI and MRE11 Analysis

PTEN= Phosphatase and tensin homolog MSI= Microsatellite instability MRE11= Double-strand break repair protein MRE11A

This trial will investigate whether the drug BMN 673 has therapeutic benefit in the treatment of advanced endometrial cancer. Nearly 8,000 patients are diagnosed with endometrial cancer in the UK every year. A significant proportion are either diagnosed with advanced disease which may be inoperable and/or metastatic (i.e spread to other organs outside the endometrium), or curable disease which relapses following first line treatment. There is no established standard of care for these patients as both chemo and hormone therapy has limited effectiveness and survival benefit. Survival rates have not improved in the past 20 years. Furthermore there are no so called 'targeted' drugs licensed for its treatment i.e. drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. This leaves an unmet need for effective systemic treatments for advanced, inoperable and metastatic endometrial cancer.

BMN 673 has been shown to be potentially effective in treating cancers known to behave similarly to endometrial disease, both in the laboratory and in Phase I studies involving patients with advanced cancers. Similarly the drug appears to be relatively tolerable. A Phase II trial such as the one proposed by this application could demonstrate activity that might lead to a new effective treatment for patients with inoperable, advanced, recurrent or metastatic endometrial cancer, while the proposed substudy also presents the possibility of discovering a subset of patients more likely to derive benefit from BMN 673.

This trial is for adult women (18 and above) with advanced, inoperable or metastatic endometrial cancer. Patients will be recruited from approximately 15 National Health Service (NHS) Trusts based in the United Kingdom (UK). The study is expected to last approximately 18-24 months in terms of recruitment time, and a maximum of 100 eligible women will be registered. All patients will receive BMN 673 until their disease worsens or their doctor decides they should stop treatment.

A Parp Inhibitor (BMN 673) for Inoperable Advanced eNDometrial cAncer

A Single Arm Phase II Trial of BMN 673 for Inoperable, Advanced Endometrial Cancer With Retrospective PTEN, MSI and MRE11 Analysis

Measured from date of first BMN 673 dose to first progression (defined using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1) or death, whichever is the sooner.

Measured from the date of first BMN 673 dose.

Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grade 3-4 toxicity; dose reductions, omissions, delays; exposure; compliance.

University College, London

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies	NCT01399840	Acute Myeloid L... Myelodysplastic... Chronic Lymphoc... Mantle Cell Lym...	BMN 673	18 Years -	Pfizer
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations	NCT01989546	Advanced Ovaria... Primary Periton... Advanced Breast... Advanced Solid ...	BMN 673	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations	NCT01989546	Advanced Ovaria... Primary Periton... Advanced Breast... Advanced Solid ...	BMN 673	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Parp Inhibitor (BMN 673) for Inoperable Advanced eNDometrial cAncer	NCT02127151	Endometrial Can...	BMN 673	18 Years -	University College, London
Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies	NCT01399840	Acute Myeloid L... Myelodysplastic... Chronic Lymphoc... Mantle Cell Lym...	BMN 673	18 Years -	Pfizer
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations	NCT01989546	Advanced Ovaria... Primary Periton... Advanced Breast... Advanced Solid ...	BMN 673	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for bmn 673

Every month we try and update this database with for bmn 673 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 bmn 673

Every month we try and update this database with for bmn 673 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 bmn 673 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.