Clinical Trials /

A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer

NCT04019327

Description:

The purpose of this study is to determine what the safest dose of talazoparib plus temozolomide for participants with metastatic castration resistant prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 19-041
  • NCT ID: NCT04019327

Conditions

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

Interventions

DrugSynonymsArms
TalazoparibTalaMetastatic Castration Resistant Prostate Cancer
TemozolomideTMZMetastatic Castration Resistant Prostate Cancer

Purpose

The purpose of this study is to determine what the safest dose of talazoparib plus temozolomide for participants with metastatic castration resistant prostate cancer.

Trial Arms

NameTypeDescriptionInterventions
Metastatic Castration Resistant Prostate CancerExperimentalParticipants have Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair
  • Talazoparib
  • Temozolomide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Safety of study treatment
Time Frame:30 days after last dose of study treatment (+/- 3 days)
Safety Issue:
Description:Toxicities will be classified by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

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

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