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Telaglenastat + Talazoparib 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: NCT04824937
Recruitment Status : Not yet recruiting
First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Collaborators:
Calithera Biosciences, Inc
Pfizer
Prostate Cancer Foundation
Information provided by (Responsible Party):
Richard J. Lee, MD, Massachusetts General Hospital

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: Telaglenastat Drug: Talazoparib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Talazoparib

Arm Intervention/treatment
Experimental: Telaglenastat + Talazoparib

During 28 day study cycles, participants will receive:

  • Telaglenastat 2x daily at a predetermined dose
  • Talazoparib 1x daily at a predetermined dose
Drug: Telaglenastat
Capsule, taken by mouth
Other Name: CB 839

Drug: Talazoparib
Capsule, taken by mouth
Other Name: Taken orally

Experimental: Telaglenastat + Talazoparib Staggered
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
Capsule, taken by mouth
Other Name: CB 839

Drug: Talazoparib
Capsule, taken by mouth
Other Name: Taken orally




Primary Outcome Measures :
  1. Rate of objective responses [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1

  2. Rate of participants with clinical benefit [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1

  3. Rate of complete responses [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1

  4. Rate of partial responses [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1

  5. Rate of participants with progressive disease [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1

  6. Rate of participants with stable disease [ Time Frame: Measured from the start of the treatment through study completion, an average of 1 year ]
    Assessed by RECIST1.1


Secondary Outcome Measures :
  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 [ Time Frame: 12 weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04824937


Contacts
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Contact: Richard J Lee, MD, PhD (617) 724-4000 rjlee@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Contact: Richard J Lee, MD, PhD    617-724-4000    rjlee@mgh.harvard.edu   
Principal Investigator: Richard J Lee, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
Calithera Biosciences, Inc
Pfizer
Prostate Cancer Foundation
Investigators
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Principal Investigator: Richard J Lee, MD, PhD Massachusetts General Hospital
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Responsible Party: Richard J. Lee, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04824937    
Other Study ID Numbers: 20-325
First Posted: April 1, 2021    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Richard J. Lee, MD, Massachusetts General Hospital:
Prostate Cancer Metastatic
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents