A Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer

Metastatic Castration-resistant Prostate Cancer Clinical Trial

— CELLO-1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04179864
• Other study ID #: EZH-1101
• Secondary ID: 2019-003649-14
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 18, 2019
• Est. completion date: June 28, 2024

Study information

• Verified date: May 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: June 28, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Tazemetostat
Tazemetostat (EPZ-6438) is a selective small-molecule inhibitor of the histone-lysine methyltransferase EZH2 gene
• 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.
• Enzalutamide
enzalutamide 160 mg (four 40 mg capsules) orally once daily

Locations

Country	Name	City	State
Belgium	Academisch Ziekenhuis Groeninge Campus Kennedylaan	Kortrijk	West Vlaanderen
Spain	Hospital de la Santa Creu i. Sant Pau	Barcelona
Spain	Hospital del Mar Parc de Salut Mar	Barcelona
Spain	Hospital Universitario de Jerez de la Frontera	Jerez De La Frontera	Cadiz
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Einstein Center for Cancer Care	Bronx	New York
United States	SCRI - Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	The Urology Center Of Colorado	Denver	Colorado
United States	Urology Associates P.C.	Hendersonville	Tennessee
United States	XCancer - Tennesee Cancer Specialists	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	SCRI - Tennessee Oncology Nashville	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	XCancer - Northwest Oncology and Hematology	Rolling Meadows	Illinois
United States	Urology San Antonio	San Antonio	Texas
United States	Genesis Healthcare Partners	San Diego	California
United States	Associated Medical Professionals of NY, PLLC - Urology	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Epizyme, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ph 1b: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)	An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	At end of Cycle 1 (each cycle is 28 days)
Primary	Ph 1b: Select the recommended phase 2 doses (RP2D) of tazemetostat for each combination	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)	1 cycle/28 days
Primary	Ph 2: Change in radiographic progression free survival (rPFS)	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	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	Phase 1b and 2: Percentage of participants with a =50% decline of Prostate Specific-Antigen (PSA50).	For participants with a baseline PSA =2.0 ug/L (ng/mL) per PCWG3 criteria	From baseline at any time on study, an average of one year
Secondary	Phase 1b and 2: Objective response rate (ORR) and best overall response (BOR) in soft tissue	According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines.	At 6 months on treatment.
Secondary	Phase 1b and 2: Disease control rate (DCR)	Assessed by radiographic progression per PCWG3 criteria, with no unequivocal clinical progression or death	At 6 months on treatment.
Secondary	Phase 1b and 2: Time to first skeletal-related event (SRE)		During screening and every 9 weeks if clinically indicated at baseline, average of one year
Secondary	Phase 1b and 2: Time to initiation of the next systemic treatment for prostate cancer (TTNT)	TTNT is defined as the time from the date of randomization to date of first documented administration of the next systemic treatment for prostate cancer.	From baseline to end of study, an average of one year
Secondary	Phase 1b and 2: Time to PSA progression (TTPP)	Defined as the duration per PCWG3 criteria in months.	From baseline to the day of PSA progression, an average one one year.
Secondary	Phase 1b and 2: Reduction in circulating tumor cells (CTC)	From a state of having a detectable number of CTCs to having an undetectable number of CTCs	From screening to 30 days after last dose
Secondary	Phase 1b and 2: CTC response rate	Defined as the percentage of participants with a =30% reduction in CTC number	From baseline to end of study, an average of one year
Secondary	Phase 1b and Phase 2: Percentage of Participants with Treatment Emergent Adverse Event (TEAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	From baseline to end of study, an average of one year
Secondary	Phase 1b and 2: AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	From baseline to end of study, an average of one year
Secondary	Phase 1b and 2:AUC0-24: area under the plasma concentration-time curve from time 0 to the time of 24 hours.	AUC_0-24 is defined as the concentration of drug over time from time zero to 24 hours.	From baseline to end of study, an average of one year
Secondary	Phase 1b and 2: Cmax: maximum plasma concentration.	Cmax is defined as the maximum observed concentration of drug.	From baseline to end of study, an average of one year
Secondary	Phase 2: Change in Functional Assessment of Cancer Therapy - Prostate (FACT-P)	Assessed by Well-being Subscale (FWB) and Prostate Cancer Subscale (PCS) scores	From baseline to end of study, an average of one year
Secondary	Phase 2: Time to definitive deterioration (TDD) in functional status and in prostate symptoms	Assessed by the FACT-P FWB and PCS scores.	From baseline to end of study, an average of one year