Clinical Trials /

Telaglenastat + Talazoparib In Prostate Cancer



The purpose of this research is to test the effectiveness of an experimental drug combination for people with metastatic castration-resistant prostate cancer (mCRPC). The names of the study drugs involved in this study are: - Telaglenastat (CB-839) - Talazoparib

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting


Phase 2

Trial Eligibility



  • Brief Title: Telaglenastat + Talazoparib In Prostate Cancer
  • Official Title: A Phase II Study of the Glutaminase Inhibitor Telaglenastat (CB-839) in Combination With the PARP Inhibitor Talazoparib in Participants With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-325
  • NCT ID: NCT04824937


  • Prostate Cancer Metastatic


TelaglenastatCB 839Telaglenastat + Talazoparib
TalazoparibTaken orallyTelaglenastat + Talazoparib


The purpose of this research is to test the effectiveness of an experimental drug combination for people with metastatic castration-resistant prostate cancer (mCRPC). The names of the study drugs involved in this study are: - Telaglenastat (CB-839) - Talazoparib

Detailed Description

      This research study is a Phase II clinical trial, researching the effectiveness of the
      combination of telaglenastat and talazoparib in participants with metastatic
      castration-resistant prostate cancer (mCRPC).

      The U.S. Food and Drug Administration (FDA) has not approved telaglenastat or the combination
      of telaglenastat and talazoparib as a treatment for any disease.

      The FDA has not approved talazoparib for metastatic castration-resistant prostate cancer
      (mCRPC) but it has been approved for other uses.

      Telaglenastat is a drug designed to stop cancer growth by blocking glutaminase activity.
      Glutaminase is an enzyme in the body that is overproduced by some cancers and can fuel cancer
      growth. Telaglenastat can lower or block glutaminase and may slow the growth or spread of
      some cancers.

      Talazoparib is a drug that interferes with the repair activity of proteins called poly
      adenosine diphosphate ribose polymerases (PARP), which are found in normal and cancer cells
      and are involved in the repair of DNA - the genetic material found in every cell. This
      interference may lead to increased amounts of DNA defects and cancer cell death which may
      help to slow the growth of cancer cells.

      The research study procedures include screening for eligibility and study treatment including
      evaluations and follow up visits.

      There are different points in this study in which participation will start. The first group
      of participants will receive the combination of telaglenastat and talazoparib for the
      entirety of the study. If telaglenastat plus talazoparib is beneficial to the first group
      this will lead to the enrollment of the next group, since telaglenastat as a single drug has
      not been evaluated in prostate cancer. The next group will receive telaglenastat alone with
      the addition of talazoparib if the disease gets worse.

      It is expected that about 30 people will take part in this research study.

Trial Arms

Telaglenastat + TalazoparibExperimentalDuring 28 day study cycles, participants will receive: Telaglenastat 2x daily at a predetermined dose Talazoparib 1x daily at a predetermined dose
  • Telaglenastat
  • Talazoparib
Telaglenastat + Talazoparib StaggeredExperimentalIf a beneficial response is seen with the Arm 1 Telaglenastat + Talazoparib combination, participants will receive telaglenastat alone 2x daily at a predetermined dose with the addition of talazoparib at 1x daily at a predetermined dose if the disease gets worse.
  • Telaglenastat
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed diagnosis
             adenocarcinoma of the prostate.

          -  Prostate cancer must be metastatic as confirmed by CT, PET scan, and/or bone scan.

          -  Prior biopsy of metastatic lesion (bone, lymph node, or visceral metastasis) with
             sufficient tissue for molecular analysis, or consent for a fresh biopsy for molecular

          -  Participants must have tested negative for homologous recombination (HR) mutations
             (including known deleterious mutations in BRCA1, BRCA2, or ATM) on a blood-based or
             tissue-based assay

          -  History of bilateral orchiectomies or ongoing GnRH agonist or antagonist

          -  Castration-resistant disease based on progression per Prostate Cancer Working Group

          -  Prior treatment for metastatic prostate cancer with docetaxel and either abiraterone
             acetate or enzalutamide, OR ineligible for or declines treatment with docetaxel,
             abiraterone acetate, or enzalutamide.

          -  Adequate renal function with a serum creatinine ≤ 2.0 mg/dL or an estimated or
             calculated creatinine clearance of > 50 mL/min (calculated using the formula of
             Cockcroft and Gault)

          -  Adequate hepatic function with total bilirubin ≤ 1.5x the upper limit of normal (ULN)
             and ALT and AST less than 3x the ULN.

          -  Adequate hematological function with ANC ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, and
             platelet count ≥ 100,000/mm3

          -  Age ≥ 18 years

          -  ECOG performance status of 0 or 1

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patients/participants with female partners of childbearing potential are eligible to
             participate if they agree to ONE of the following for the duration of the study:

               -  Are abstinent from penile-vaginal intercourse as their usual and preferred
                  lifestyle (abstinent on a long-term and persistent basis) and agree to remain
                  abstinent for duration of the study.

               -  Agree to use a male condom and have their partner use a contraceptive method with
                  a failure rate of <1% per year (intrauterine device or hormonal implant).

          -  Patients/participants must refrain from donating sperm for the duration of the study.

          -  Patients/participants with a pregnant or breastfeeding partner must agree to remain
             abstinent from penile-vaginal intercourse or use a male condom during each episode of
             penile penetration for the duration of the study.

        Exclusion Criteria:

          -  Participants who have received more than two prior chemotherapy regimens for
             metastatic castration-resistant prostate cancer.

          -  Participants who have any previous treatment with PARP inhibitors

          -  Participants who are receiving any other investigational agents.

          -  Participants who have received radiation therapy within 2 weeks or radionuclide
             treatment within 6 weeks prior to registration on this study

          -  Participants with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to telaglenastat or talazoparib

          -  Concurrent use of moderate or strong CYP3A4 inducers or inhibitors, which could affect
             talazoparib plasma concentrations

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or
             Hepatitis C.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of objective responses
Time Frame:Measured from the start of the treatment through study completion, an average of 1 year
Safety Issue:
Description:Assessed by RECIST1.1

Secondary Outcome Measures

Measure:Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time Frame:12 weeks
Safety Issue:
Description:The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade. This analysis will be performed overall and separately for Cohort 1 and 2. Within a given patient, a given adverse event will be counted only once at the highest grade.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Prostate Cancer Metastatic

Last Updated

April 1, 2021