Prostate Cancer
Conditions
Keywords
Prostate cancer, Radical prostatectomy, RP
Brief summary
This study is an open-label, single-arm, pilot, perioperative study of EZH2 inhibition in patients undergoing Radical Prostatectomy (RP). The EZH2 inhibition is intended to increase the sensitivity of the underlying tumor to the patient's immune system. Given the absence of data in this setting, we propose to pilot this experience with 4 weeks of tazemetostat at doses known to be clinically safe and effective at inducing clinical effects via inhibition of EZH2 as established for follicular lymphoma and epithelioid sarcoma: 800 mg twice daily with or without food. Prior to tazemetostat, blood will be collected (4 tubes) for immune cells, Circulating Tumor Cells, and plasma. This will be repeated at the time of RP. RP tissues will be collected. Additionally, patients will have a week lead-in to wear a FitBit Charge 5TM device (or similar model) to continuously monitor physical activity from baseline up until end of study. The start of the week lead-in will be considered the baseline visit. Subjects will also be asked to continue wearing the device until end of study and option to continue for up to 2 years after end of study in follow-up.
Interventions
DRUGTazverik
Tazemetostat (Tazverik) 200 mg oral tablets; 800 mg by mouth twice daily for 28 days
Sponsors
Epizyme, Inc.
Edwin Posadas, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men electing to undergo radical prostatectomy with preoperative tissue available * Able to take oral medications * Age ≥18 years * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Adequate organ function * Men with partners of childbearing potential, must have had a successful vasectomy (with medically confirmed lack of sperm that are alive) OR must either practice complete abstinence or agree to use adequate contraception * Inclusion criteria for remote monitoring component of study with Fitbit only (failure to meet inclusion criterion for Fitbit-monitoring portion of study should not preclude participating in treatment trial): Access to a device (e.g., smart phone, tablet) that has the capability to sync to the Fitbit. Note: access can be via family member, friend, caregiver, or study-designated device provided by study member
Exclusion criteria
* Active intercurrent illness or malignancy requiring therapy outside of prostate cancer * History of bleeding disorders * Concurrent use of anti-platelet agents or therapeutic anticoagulants with the exception of low-dose aspirin (81 mg daily) or NSAIDs for pain/inflammation. Concurrent use of strong and moderate CYP3A inhibitors and inducers * Subjects who have previously received tazemetostat * Currently participating in a study using an investigational, medicinal anti-cancer agent within 4 weeks prior to first dose of tazemetostat *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events, serious adverse events, and treatment-related adverse events. | From start of study treatment until confirmation of disease progression, intolerable toxicities, or withdrawal of consent, whichever came first. Assessed up to 30 days following last dose of study treatment. | Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Proportion of patients able to undergo surgery | At time of surgery | — |
| Proportion of patients with Grade 3 or above treatment related adverse events | From start of study treatment until confirmation of disease progression, intolerable toxicities, or withdrawal of consent, whichever came first. Assessed up to 30 days following last dose of study treatment. | Grade 3 or above treatment related adverse events as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Proportion of patients with evaluable tissue specimens following tazemetostat | At time of surgery | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Progression Free Survival | From the start of study treatment until documented progression, or death due to any cause. Assessed up to 5 years. | Defined by a detectable post-operative prostate-specific antigen (PSA) |
Countries
United States
Outcome results
None listed