A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer

NCT04019327 | Completed Phase 1 FDA Drug

• 1 other identifier: 19-041
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to determine what the safest dose of talazoparib plus temozolomide for participants with metastatic castration resistant prostate cancer. The purpose of Phase II is to test the efficacy (effectiveness) of talazoparib and temozolomide at the maximum tolerated dose, which was determined to be 1mg talazoparib and 75mg/m² temozolomide in the Phase Ib portion of this study.

Conditions

Prostate Cancer; Prostate Adenocarcinoma; Prostate Neoplasm; Prostate Cancer Metastatic; Castration-resistant Prostate Cancer

Keywords

talazoparib; temozolomide; Prostate cancer; Memorial Sloan Kettering Cancer Center; 19-041

Outcome Measures

Primary Outcomes (2)

• Phase I: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])

  Toxicities will be classified by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0).

  30 days after last dose of study treatment (+/- 3 days)

• Phase II: Overall Response Rate

  Overall best response rate (confirmed CT or PR) will be calculated according to RECIST v1.1

  30 days after last dose of study treatment (+/- 3 days)

Study Arms (1)

Metastatic Castration Resistant Prostate Cancer

EXPERIMENTAL

Participants have Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair

Drug: Talazoparib; Drug: Temozolomide

Interventions

Talazoparib DRUG

Phase I maximum tolerated dose portion: Level 1, 2, 3 - 1 mg QD Days 1-6 Level 4, 5 - 1.25 mg QD Days 1-6 Level 6 - 1.5 mg QD Days 1-6

Also known as: Tala

Metastatic Castration Resistant Prostate Cancer

Temozolomide DRUG

Phase I maximum tolerated dose portion: Level 1 - 37.5 mg/m2 QD Days 2-8 Level 2 - 75 mg/m2 QD Days 2-8 Level 3 \& 4 - 100 mg/m2 QD Days 2-8 Level 5 \& 6 - 125 mg/m2 QD Days 2-8

Also known as: TMZ

Metastatic Castration Resistant Prostate Cancer

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information or have their legally authorized representative provide written informed consent. A signed informed consent must be obtained prior to performing screening procedures.
• NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
• Males 18 years of age or above
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Bilateral orchiectomy or ongoing androgen deprivation therapy with a GnRH agonist/antagonist (surgical or medical castration)
• Progression of mCRPC on treatment with at least 1 second generation hormonal agent (e.g., enzalutamide and/or abirateroneacetate/prednisone)
• Documented progressive mCRPC based on at least one of the following criteria:
• PSA progression defined as at least 2 rises in PSA with a minimum of a 1-week interval
• ng/mL is the minimal starting value if confirmed rise is only indication of progression
• Soft-tissue progression per RECISTv1.1
• Progression of bone disease (evaluable disease) or tow or more new bone lesions by bone scan
• Metastatic disease documented by bone lesions on whole-body radionuclide bone scan or soft tissue disease by computed tomography/magnetic-resonance imaging (CT/MRI).
• Consent to a fresh tumor biopsy during screening or have sufficient archival tumor tissue available for molecular profile and biomarker analyses
• ECOG status of 0 or 1 (Appendix A: Performance Status Criteria)
• Serum testosterone \</= 50mg/dL at screening

You may not qualify if:

• Prior treatment with a taxane-based chemotherapy for mCRPC (prior treatment with a taxane-based chemotherapy for metastatic non-castrate prostate cancer is permitted)
• Prior treatment with a PARP inhibitor, platinum, cyclophosphamide, mitozantrone chemotherapy, ortemozolmide
• Patient has received radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) of treatment start
• Documented carrier of a pathogenic or likely pathogenic germline or somatic mutation in BRCA 1, BRC 2 or ATM or known carrier (pathogenic or likely pathogenic) or one of the following DNA Damage Repair genes considered as sensitizing tumors to PARP inhibitors: FANCA, CHECK2, PALB2, MRE11A, NBN, RAD51C, ATR, MLH1, and CDK12. Testing is required for BRCA 1, BRCA 1, or ATM. If a patient has had next generation sequencing that did not include FANCA, CHECK2, PALB2, MRE11A, NBN, RAD51C, ATR, MLH1, or CDK12 he will not be excluded from the study if status is unknown.
• Note, if testing is germline negative, somatic testing is still required. If the patient is germline positive, the patient is ineligible.
• Use of systemic hormonal (except for GnRH analog), biologic, radium-223, or any investigational therapy for treatment of metastatic prostate cancer within 4 weeks prior to treatment start. Exceptions include abiraterone, which may not have been administered within 2 weeks of treatment start.
• Use of Lutetium (177Lu) vipivotide tetraxetan within 4 weeks prior to treatment start.
• Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, or cardiac disease that would, in the opinion of the investigator, make this protocol unreasonably hazardous to the patient.
• Known or suspected brain metastasis or active leptomeningeal disease.
• Symptomatic or impending spinal cord compression or cauda equine syndrome
• Diagnosis of myelodysplastic syndrome (MDS)
• History of another cancer within 2 years of treatment start with the exception of nonmelanoma skin cancers or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the Sponsor
• Use of any prohibited concomitant medications (Appendix C: Medications With the Potential for Drug-Drug Interactions) within 14 days prior to the first dose of talazoparib
• Grade \> 2 treatment-related toxicity unresolved from prior therapy
• Known allergy to any of the compounds under investigation

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (9)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited protocol activity)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Lehigh Valley Health Network (Data Collection Only)

Allentown, Pennsylvania, 18103, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

talazoparib; Temozolomide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Karen Autio, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 15, 2019
• Study Start: July 11, 2019
• Primary Completion: December 4, 2025
• Study Completion: December 4, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (9)