Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes

NCT02286687 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2013-0961NCI-2014-02494
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, do not respond to treatment, or have spread to other parts of the body, and have alterations in the breast cancer, early onset (BRCA) genes. Talazoparib may cause tumor cells to die by blocking an enzyme that protects the tumor cells from damage.

Conditions

Advanced Malignant Neoplasm; ATM Gene Mutation; BRCA2 Gene Mutation; PALB2 Gene Mutation; BRCA1 Gene Mutation; Metastatic Malignant Neoplasm; Recurrent Malignant Neoplasm; Refractory Malignant Neoplasm

Outcome Measures

Primary Outcomes (1)

• Clinical benefit by Response Evaluation Criteria in Solid Tumors 1.1

  Evaluated separately in each cohort. Calculated using posterior probabilities along with corresponding credible intervals.

  Up to 1 year

Secondary Outcomes (3)

• Progression free survival

  Up to 1 year

• Overall survival

  Up to 1 year

• Duration of response

  Up to 1 year

Other Outcomes (10)

• Molecular markers that may predict clinical benefit

  Baseline

• Pharmacodynamic markers in blood and plasma that may predict outcome

  Up to week 4

• BRCA1/2 alterations in archival tissue

  Baseline

Study Arms (1)

Treatment (talazoparib)

EXPERIMENTAL

Patients receive talazoparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Talazoparib

Interventions

Pharmacological Study OTHER

Correlative studies

Treatment (talazoparib)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673

Treatment (talazoparib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (talazoparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic cancer that is refractory to standard therapy or has relapsed after standard therapy
• Patients must have one of the following: somatic mutations or deletions in BRCA1 or BRCA2; genomic alterations in other BRCA pathway genes (subcohorts: a. ATM, b. PALB2, c. other genes, e.g. Fanconi Anemia genes, ARID1A, MER11, RAD50, NBS1, ATR; amplification of EMSY); or germline mutation in BRCA1 or BRCA 2 (not breast or ovarian cancer)
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Absolute neutrophil count \>= 1500/mL
• Platelets \>= 100,000/mL
• Hemoglobin \>= 9 g/dL (or \>= 5.6 mmol/L)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) (or glomerular filtration rate \[GFR\] \>= 60 ml/min for patients with creatinine \> 1.5 x ULN)
• Serum total bilirubin =\< 1.5 x ULN (direct bilirubin =\< ULN if total bilirubin \[bili\] \> 1.5 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (or =\< 5 x ULN if liver metastases \[mets\])
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants; activated PTT (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Patients must be \>= 4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation
• Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea); patients should not become pregnant or breastfeed while on this study; sexually active patients must agree to use dual contraception for the duration of study participation and for 120 days after the last dose of talazoparib
• Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures
• Patients need to have biopsiable disease to enroll on cohort 1-2; patients eligible for cohort 3 with a germline BRCA alteration can be enrolled even if they do not have biopsiable disease

You may not qualify if:

• Patients who are pregnant or breastfeeding
• Prior treatment with a PARP inhibitor
• Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
• Inability or unwillingness to swallow pills
• Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization
• Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g. gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)
• Inability to comply with the study and follow-up procedures
• History of cerebrovascular accident (CVA), myocardial infarction or unstable angina within the previous 6 months before starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless or clinical stability

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence; Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Sarina A Piha-Paul

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 10, 2014
• Study Start: December 22, 2014
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

US (1)