Description:
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
Title
- 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
Conditions
- Prostate Cancer Metastatic
Interventions
Drug | Synonyms | Arms |
---|
Telaglenastat | CB 839 | Telaglenastat + Talazoparib |
Talazoparib | Taken orally | Telaglenastat + Talazoparib |
Purpose
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
Name | Type | Description | Interventions |
---|
Telaglenastat + Talazoparib | Experimental | During 28 day study cycles, participants will receive:
Telaglenastat 2x daily at a predetermined dose
Talazoparib 1x daily at a predetermined dose | |
Telaglenastat + Talazoparib Staggered | Experimental | 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. | |
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
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.
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. |
Details
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