Description:
A phase 1b/2 study to examine taz in combination with enz or abi/pred in patients with
metastic castration resistant prostate cancer
Title
- Brief Title: Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Subjects With Castration Resistant Prostate Cancer Who Have Not Received Chemotherapy
- 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
Clinical Trial IDs
- ORG STUDY ID:
EZH-1101
- NCT ID:
NCT04179864
Conditions
- Metastatic Prostate Cancer
Interventions
Drug | Synonyms | Arms |
---|
Tazemetostat | EPZ-6438, E7438 | Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone |
Abiraterone/prednisone | Zytiga | Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone |
Enzalutamide | Xtandi | Phase 1b: Tazemetostat in Combination with Enzalutamide |
Purpose
A phase 1b/2 study to examine taz in combination with enz or abi/pred in patients with
metastic castration resistant prostate cancer
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1b: Tazemetostat in Combination with Abiraterone/Prednisone | Experimental | In Phase 1b, Abiraterone/prednisone will be administered on cycle 1 day 1 and Tazemetostat on cycle 1 day 2 | - Tazemetostat
- Abiraterone/prednisone
|
Phase 1b: Tazemetostat in Combination with Enzalutamide | Experimental | In Phase 1b, Enzalutamide will be administered on cycle 1 day 1 and Tazemetostat on cycle 1 day 2 | |
Phase 2: Tazemetostat in Combination with Enzalutamide | Experimental | In Phase 2, Enzalutamide and Tazemetostat will be administered on cycle 1 day 1 | |
Phase 2: Enzalutamide only | Active Comparator | In Phase 2, Enzalutamide will be administered on cycle 1 day 1 | |
Eligibility 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | Confirmed prostate-specific antigen (PSA) responses will be defined as ≥50% reductions in PSA from baseline to lowest post baseline PSA result |
Measure: | 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) |
Safety Issue: | |
Description: | PSA progression is defined as a ≥25% increase from baseline to the day of PSA progression per PCWG3 criteria |
Measure: | 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. |
Safety Issue: | |
Description: | Time from randomization to first SRE will be assessed. |
Measure: | 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) |
Safety Issue: | |
Description: | Assess objective response rate (ORR) per PCWG3 criteria and RECIST 1.1 guidelines |
Measure: | 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 |
Safety Issue: | |
Description: | Assess disease control rate (DCR), no radiographic progression per PCWG3 criteria and no unequivocal clinical progression or death |
Measure: | 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) |
Safety Issue: | |
Description: | Assess the PK of tazemetostat from collection of blood draws |
Measure: | 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) |
Safety Issue: | |
Description: | Assess the PK of enzalutamide from collection of blood draws |
Measure: | 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) |
Safety Issue: | |
Description: | Assess the PK of abiraterone/prednisone from collection of blood draws |
Measure: | 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) |
Safety Issue: | |
Description: | 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 |
Measure: | 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) |
Safety Issue: | |
Description: | Assess CTC response rate as defined by a ≥30% reduction in CTC number from baseline. |
Measure: | 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) |
Safety Issue: | |
Description: | Quality of Life (QoL) as assessed by changes from baseline in FACT-P Functional Well-being Subscale (FWB) |
Measure: | 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) |
Safety Issue: | |
Description: | Quality of Life (QoL) as assessed by changes from baseline in Brief Pain Inventory (BPI) short form |
Measure: | 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) |
Safety Issue: | |
Description: | Quality of Life (QoL) as assessed by changes from baseline in EQ-5D-5L visual analogue scale. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Epizyme, Inc. |
Trial Keywords
- metastatic castration resistant prostate cancer
- tazemetostat
- EPZ-6438
- E7438
- enzalutamide
- abiraterone
- Prednisone
- Zytiga
- Xtandi
Last Updated
July 1, 2021