Clinical trial NCT04179864: A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
Official title: CELLO-1: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Keywords: metastatic castration resistant prostate cancer
tazemetostat
EPZ-6438
E7438
enzalutamide
abiraterone
Prednisone
Zytiga
Xtandi
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2019-11-27
Enrollment: 102
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a global, multi-center, open-label, randomized phase 1b/2, 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.


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 antagonist including enzalutamide, apalutamide, darolutamide, and proxalutamide, etc.
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.

Primary outcomes:
measure: Ph 1b: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
timeFrame: At end of Cycle 1 (each cycle is 28 days)
measure: Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination
timeFrame: 1 cycle/28 days
measure: Ph 2: Change in radiographic progression free survival (rPFS)
timeFrame: 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)
Secondary outcomes:
measure: Phase 1b and 2: Percentage of participants with a ≥50% decline of Prostate Specific-Antigen (PSA50).
timeFrame: From baseline at any time on study, an average of one year
measure: Phase 1b and 2: Objective response rate (ORR) and best overall response (BOR) in soft tissue
timeFrame: At 6 months on treatment.
measure: Phase 1b and 2: Disease control rate (DCR)
timeFrame: At 6 months on treatment.
measure: Phase 1b and 2: Time to first skeletal-related event (SRE)
timeFrame: During screening and every 9 weeks if clinically indicated at baseline, average of one year
measure: Phase 1b and 2: Time to initiation of the next systemic treatment for prostate cancer (TTNT)
timeFrame: From baseline to end of study, an average of one year
measure: Phase 1b and 2: Time to PSA progression (TTPP)
timeFrame: From baseline to the day of PSA progression, an average one one year.
measure: Phase 1b and 2: Reduction in circulating tumor cells (CTC)
timeFrame: From screening to 30 days after last dose
measure: Phase 1b and 2: CTC response rate
timeFrame: From baseline to end of study, an average of one year
measure: Phase 1b and Phase 2: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)
timeFrame: From baseline to end of study, an average of one year
measure: Phase 1b and 2: AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
timeFrame: From baseline to end of study, an average of one year
measure: Phase 1b and 2:AUC0-24: area under the plasma concentration-time curve from time 0 to the time of 24 hours.
timeFrame: From baseline to end of study, an average of one year
measure: Phase 1b and 2: Cmax: maximum plasma concentration.
timeFrame: From baseline to end of study, an average of one year
measure: Phase 2: Change in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
timeFrame: From baseline to end of study, an average of one year
measure: Phase 2: Time to definitive deterioration (TDD) in functional status and in prostate symptoms
timeFrame: From baseline to end of study, an average of one year
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Genesis Healthcare Partners
state: California
city: Denver
country: United States
facility: The Urology Center Of Colorado
state: Colorado
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Rolling Meadows
country: United States
facility: XCancer - Northwest Oncology and Hematology
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Central Valley
state: Nevada
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY, PLLC - Urology
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: SCRI - Tennessee Oncology Chattanooga
state: Tennessee
city: Hendersonville
country: United States
facility: Urology Associates P.C.
state: Tennessee
city: Knoxville
country: United States
facility: XCancer - Tennesee Cancer Specialists
state: Tennessee
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology Nashville
state: Tennessee
city: San Antonio
country: United States
facility: Urology San Antonio
state: Texas
city: Kortrijk
country: Belgium
facility: Academisch Ziekenhuis Groeninge Campus Kennedylaan
state: West Vlaanderen
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
state: Cadiz
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i. Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar Parc de Salut Mar
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: