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A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04019327
Recruitment Status : Recruiting
First Posted : July 15, 2019
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE July 11, 2019
First Posted Date  ICMJE July 15, 2019
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE July 11, 2019
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • Phase I: Safety of study treatment [ Time Frame: 30 days after last dose of study treatment (+/- 3 days) ]
    Toxicities will be classified by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0).
  • Phase II: Overall Response Rate [ Time Frame: 30 days after last dose of study treatment (+/- 3 days) ]
    Overall best response rate (confirmed CT or PR) will be calculated according to RECIST v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer
Official Title  ICMJE A Phase Ib/II Study of Intermittent Talazoparib Plus Temozolomide in Subjects With Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Prostate Adenocarcinoma
  • Prostate Neoplasm
  • Prostate Cancer Metastatic
  • Castration-resistant Prostate Cancer
Intervention  ICMJE
  • 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 Name: 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 Name: TMZ
Study Arms  ICMJE Experimental: Metastatic Castration Resistant Prostate Cancer
Participants have Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair
Interventions:
  • Drug: Talazoparib
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2019)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 y 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

  • Subjects 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
  • Subject 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 subject 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 subject is germline positive, the subject in 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.
  • 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 subject.
  • 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 within 14 days prior to the first dose of talazoparib (Note, use of P-gp inhibitors that may be taken with caution at the investigator's discretion will not exclude subjects from the trial)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Karen Autio, MD 646-422-4632 AutioK@mskcc.org
Contact: Howard Scher, MD 646-888-4878 scherh@mskcc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04019327
Other Study ID Numbers  ICMJE 19-041
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Karen Autio, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP