A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer

A Phase Ib/II Study of Intermittent Talazoparib Plus Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Castration-resistant Prostate Cancer; Prostate Adenocarcinoma; Prostate Cancer Metastatic; Prostate Neoplasm
• Intervention / Treatment: Drug: Talazoparib; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Karen Autio, MD; Phone Number: 646-422-4632; Email: AutioK@mskcc.org
• Study Contact Backup: Name: Howard Scher, MD; Phone Number: 646-888-4878; Email: scherh@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Commack (Limited protocol activity)
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Karen Autio, MD; Phone Number: 646-422-4632
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Recruiting
      • Lehigh Valley Health Network (Data Collection Only)
      • Contact: Paul Palyca, MD; Phone Number: 610-402-7880
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Active, not recruiting
      • University of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin
      • Contact: Christos Kyriakopoulos, MD; Phone Number: 608-263-0786

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
  • 1.0 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
• Adequate organ function with acceptable initial laboratory values within 14 days of treatment start:

Absolute neutrophil count (ANC): >/= 1,500/ul Hemoglobin: >/= 9g/dL Platelet count: >/= 100,00/ul Creatinine: >/= 60 mL/min estimated using the Cockcroft-Gault equation Potassium: >/= 3.5 mmol/L (within institutional normal range) Bilirubin: </= 1.5 ULN (unless documented Gilbert's disease) SGOT(AST): </= 2.5 x ULN SGPT (ALT): </= 2.5 x ULN

• Patients must agree to use a highly effective method of contraception (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence during treatment, and for at least 7 months after completing therapy. Furthermore, male patients with female partners of reproductive potential and pregnant partners must use a condom (even after vasectomy), during treatment and for at least 4 months after the final dose. Sperm donation is prohibited during the study and for 30 days after the last dose of study drug. Female partners must use hormonal or barrio contraception unless postmenopausal or abstinent.

Exclusion Criteria:

• 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
• Any other condition which, in the opinion of the investigator, would preclude participation in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metastatic Castration Resistant Prostate Cancer; Participants have Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair	Drug: Talazoparib; 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; Other Names: Tala; Drug: Temozolomide; 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; Other Names: TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Karen Autio, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 15, 2019

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Prostate cancer; Memorial Sloan Kettering Cancer Center; temozolomide; talazoparib; 19-041
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Poly(ADP-ribose) Polymerase Inhibitors; Temozolomide; Talazoparib
• Other Study ID Numbers: 19-041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: • Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes