Metastatic Castration-resistant Prostate Cancer Clinical Trial
— CELLO-1Official 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
Verified date | April 2024 |
Source | Ipsen |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Epizyme, Inc. |
United States, Belgium, Spain,
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 |
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