Telaglenastat + Talazoparib In Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Drug: Telaglenastat
* Drug: Talazoparib


Participation Criteria
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Eligibility Criteria
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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 analysis 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 2.21 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaglenastat + Talazoparib<br>During 28 day study cycles, participants will receive: Telaglenastat 2x daily at a predetermined dose Talazoparib 1x daily at a predetermined dose | Drug: Telaglenastat<br>* Capsule, taken by mouth<br>* Other names: CB 839;Drug: Talazoparib<br>* Capsule, taken by mouth<br>* Other names: Taken orally;|
| Experimental: Telaglenastat + Talazoparib Staggered<br>If 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. | Drug: Telaglenastat<br>* Capsule, taken by mouth<br>* Other names: CB 839;Drug: Talazoparib<br>* Capsule, taken by mouth<br>* Other names: Taken orally;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of objective responses | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 
| Rate of participants with clinical benefit | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 
| Rate of complete responses | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 
| Rate of partial responses | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 
| Rate of participants with progressive disease | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 
| Rate of participants with stable disease | Assessed by RECIST1.1 | Measured from the start of the treatment through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | 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. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer Metastatic