Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Subjects With Castration Resistant Prostate Cancer Who Have Not Received Chemotherapy

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: NCT04179864
Recruitment Status : Recruiting
First Posted : November 27, 2019
Last Update Posted : May 26, 2021
Sponsor:
Information provided by (Responsible Party):
Epizyme, Inc.

Brief Summary:
A phase 1b/2 study to examine taz in combination with enz or abi/pred in patients with metastic castration resistant prostate cancer

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Drug: Tazemetostat Drug: Abiraterone/prednisone Drug: Enzalutamide Phase 1 Phase 2

Detailed Description:
This is a global, multi-center, open-label, randomized phase 1b, active-controlled safety and efficacy study of oral administration of tazemetostat in combination with enzalutamide or abiraterone/prednisone (phase 1b) versus enzalutamide or abiraterone/prednisone alone in asymptomatic or mildly symptomatic subjects with progressive, metastatic castration-resistant prostate cancer (mCRPC) who have progressed on either abiraterone acetate, enzalutamide, or apalutamide or who are second generation anti-androgen treatment naive, and who have not received chemotherapy for mCRPC. This study is designed to determine the recommended phase 2 doses (RP2D) of tazemetostat in combination with either enzalutamide or abiraterone/prednisone, based on safety, tolerability, pharmacokinetic, pharmacodynamic, and efficacy profiles.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Open-Label Study Evaluating Tazemetostat in Combination With Enzalutamide or Abiraterone/Prednisone in Chemotherapy Naive Subjects With Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : September 26, 2019
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone
In Phase 1b, Abiraterone/prednisone will be administered on cycle 1 day 1 and Tazemetostat on cycle 1 day 2
Drug: Tazemetostat
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
Other Names:
  • EPZ-6438
  • E7438

Drug: Abiraterone/prednisone
1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily in combination with prednisone 5 mg administered orally twice daily.
Other Name: Zytiga

Experimental: Phase 1b: Tazemetostat in Combination with Enzalutamide
In Phase 1b, Enzalutamide will be administered on cycle 1 day 1 and Tazemetostat on cycle 1 day 2
Drug: Tazemetostat
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
Other Names:
  • EPZ-6438
  • E7438

Drug: Enzalutamide
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Other Name: Xtandi

Experimental: Phase 2: Tazemetostat in Combination with Enzalutamide
In Phase 2, Enzalutamide and Tazemetostat will be administered on cycle 1 day 1
Drug: Tazemetostat
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
Other Names:
  • EPZ-6438
  • E7438

Drug: Enzalutamide
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Other Name: Xtandi

Active Comparator: Phase 2: Enzalutamide only
In Phase 2, Enzalutamide will be administered on cycle 1 day 1
Drug: Enzalutamide
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Other Name: Xtandi




Primary Outcome Measures :
  1. Ph 1b: Determine the safety and tolerability of each of the combinations [ Time Frame: Assessed at end of Cycle 1 (each cycle is 28 days) ]
    Assess safety and tolerability of Tazemetostat in combination with enzalutamide or with abiraterone/prednisone by reviewing incidence and severity of treatment-emergent adverse events (AEs) qualifying as protocol-defined DLTs in Cycle 1Safety and tolerability of Tazemetostat in combination with enzalutamide or with abiraterone/prednisone

  2. Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination [ Time Frame: 1 cycle/28 days ]
    Based on pharmacokinetic (PK) and pharmacodynamic parameters as well as efficacy and the overall tolerability of each of the combinations (tazemetost with enzalutamide or tazemetostat with abiraterone/prednisone)

  3. Ph 2: Determine the benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone by assessing change in radiographic progression free survival [ Time Frame: Day 1 of Cycles 3, 5, 7, 10, and 13, and every 12 weeks after Cycle 13 for 1 year (each cycle is 28 days) ]
    Assessed by change radiographic progression free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for progression in bone or in soft tissue


Secondary Outcome Measures :
  1. Determine benefit of combining tazemetostat with enzalutamide or abiraterone/prednisone (phase 1b) and benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone (phase 2) - PSA Change [ Time Frame: Assessed at Day 1 of every cycle for an average of one year (each cycle is 28 days) ]
    Confirmed prostate-specific antigen (PSA) responses will be defined as ≥50% reductions in PSA from baseline to lowest post baseline PSA result

  2. Determine benefit of combining tazemetostat with enzalutamide or abiraterone/prednisone (phase 1b) and benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone (phase 2) - PSA Change [ Time Frame: Assessed at Day 1 of every cycle for an average of one year (each cycle is 28 days) ]
    PSA progression is defined as a ≥25% increase from baseline to the day of PSA progression per PCWG3 criteria

  3. Determine benefit of combining tazemetostat with enzalutamide or abiraterone/prednisone (phase 1b) and benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone (phase 2) - First Skeletal-Related Event (SRE) [ Time Frame: During screening and every 9 weeks if clinically indicated at baseline, average of one year. ]
    Time from randomization to first SRE will be assessed.

  4. Determine benefit of combining tazemetostat with enzalutamide or abiraterone/prednisone (phase 1b) and benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone (phase 2) - ORR [ Time Frame: Assessed at Day 1 of every cycle for an average of one year (each cycle is 28 days) ]
    Assess objective response rate (ORR) per PCWG3 criteria and RECIST 1.1 guidelines

  5. Determine benefit of combining tazemetostat with enzalutamide or abiraterone/prednisone (phase 1b) and benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone (phase 2) - DCR [ Time Frame: Assessed at 6 months on treatment ]
    Assess disease control rate (DCR), no radiographic progression per PCWG3 criteria and no unequivocal clinical progression or death

  6. Evaluate the safety and tolerability of the combination of study drugs by assessing PK data [ Time Frame: Phase 1b PK of Tazemetostat will be assessed on Day 1 of Cycles 1 and 2. Phase 2 PK of Tazemetostat will be assessed on Day 1 of Cycles 2, 3, 5 and 10. (each cycle is 28 days) ]
    Assess the PK of tazemetostat from collection of blood draws

  7. Evaluate the safety and tolerability of the combination of study drugs by assessing PK data [ Time Frame: Phase 1b PK of enzalutamide will be assessed on Day 1 of Cycles 1 and 2. Phase 2 PK enzalutamide will be assessed on Day 1 of Cycles 2, 3, 5 and 10. (each cycle is 28 days) ]
    Assess the PK of enzalutamide from collection of blood draws

  8. Evaluate the safety and tolerability of the combination of study drugs by assessing PK data [ Time Frame: Phase 1b PK of abiraterone/prednisone will be assessed on Day 1 of Cycles 1 and 2. (each cycle is 28 days) ]
    Assess the PK of abiraterone/prednisone from collection of blood draws

  9. Assess the rate of reducing circulating tumor cells (CTC) [ Time Frame: Assessed at screening, on Day 1 of Cycles 1, 2, 3, 4, 5, 7, 10 and 13 (each cycle is 28 days) and post-treatment (30 days after last dose) ]
    Assess the rate of reducing circulating tumor cells (CTC) from a state of having a detectable number of CTCs to having an undetectable number of CTCs

  10. Assess CTC response rate [ Time Frame: Assessed at screening, Day 1 of Cycles 1, 2, 3, 4, 5, 7, 10, 13 (each cycles is 28 days), and post-treatment (30 days after last dose) ]
    Assess CTC response rate as defined by a ≥30% reduction in CTC number from baseline.

  11. PHASE 2 ONLY: To determine the benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone, quality of life (QoL) will be assessed. [ Time Frame: Assessed at screening, Day 1 of Cycles 3, 5, 7, 10, 13 (each cycle is 28 days), and post-treatment (30 days after last dose) ]
    Quality of Life (QoL) as assessed by changes from baseline in FACT-P Functional Well-being Subscale (FWB)

  12. PHASE 2 ONLY: To determine the benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone, quality of life (QoL) will be assessed. [ Time Frame: Assessed at screening, Day 1 of Cycles 3, 5, 7, 10, 13 (each cycle is 28 days), and post-treatment (30 days after last dose) ]
    Quality of Life (QoL) as assessed by changes from baseline in Brief Pain Inventory (BPI) short form

  13. PHASE 2 ONLY: To determine the benefit of combining tazemetostat with enzalutamide when compared to enzalutamide alone, quality of life (QoL) will be assessed. [ Time Frame: Assessed at screening, Day 1 of Cycles 3, 5, 7, 10, 13 (each cycle is 28 days), and post-treatment (30 days after last dose) ]
    Quality of Life (QoL) as assessed by changes from baseline in EQ-5D-5L visual analogue scale.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age at the time of consent ≥ 18 years.
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix
  3. Life expectancy of > 3 months.
  4. Histologically or cytologically confirmed adenocarcinoma of the prostate. Small cell or neuroendocrine tumors of the prostate are also permitted.
  5. Progressive disease in the setting of medical or surgical castration (ie, castration- resistant prostate cancer [CRPC]) by PCWG3 criteria for study entry.

    • Evidence of disease progression by rising PSA or
    • Soft tissue progression per RECIST 1.1 or
    • Evidence of disease progression by observation of 2 new bone lesions since the initiation of last systemic therapy.
  6. Metastatic prostate cancer disease, documented by the following imaging

    • Bone lesions on bone scan (per PCWG3) or by soft tissue disease (per RECIST 1.1) by CT/MRI imaging Must have undergone bilateral orchiectomy or be willing to continue GnRH analogue or antagonist.

  7. Prior treatment with a second-generation androgen inhibitor as follows:

    • For phase 1b, EITHER Previously untreated with or progressed on a second generation androgen inhibitor (abiraterone, enzalutamide, or apalutamide) OR progressed on a second generation inhibitor (inhibitor (abiraterone, enzalutamide, or apalutamide)
    • For phase 2 randomized component (i.e, enzalutamide- containing treatment arms) of the study, previously progressed on abiraterone.

Exclusion Criteria:

  1. Known symptomatic brain metastases
  2. Treatment with any of the following for prostate cancer within the indicated timeframe prior to day 1 of starting study treatment:

    • First generation: AR antagonists (eg, bicalutamide, nilutamide, flutamide) within 4 weeks.
    • 5-alpha-reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol), or progesterones within 2 weeks.
    • Chemotherapy (except as permitted in inclusion criteria #10) within 3 weeks.
    • Prior radionuclide therapy within 4 weeks.
    • Another interventional product or standard agent in a clinical study within 28 days prior to the first planned dose of Tazemetostat
    • For phase 2 subjects to be randomized to one of the enzalutamide treatment arms only, prior treatment with the second-generation androgen inhibitor enzalutamide
  3. Severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment
  4. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2.

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): NCT04179864


Contacts
Layout table for location contacts
Contact: Shefali Agarwal, MD 617-229-7575 clinicaltrials@epizyme.com
Contact: Daniel Powers, DO 978-289-8488

Locations
Show Show 24 study locations
Sponsors and Collaborators
Epizyme, Inc.
Layout table for additonal information
Responsible Party: Epizyme, Inc.
ClinicalTrials.gov Identifier: NCT04179864    
Other Study ID Numbers: EZH-1101
First Posted: November 27, 2019    Key Record Dates
Last Update Posted: May 26, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Epizyme, Inc.:
metastatic castration resistant prostate cancer
tazemetostat
EPZ-6438
E7438
enzalutamide
abiraterone
Prednisone
Zytiga
Xtandi
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents