Follicular Lymphoma (FL), Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC)
Conditions
Keywords
EZH2, enhancer of zeste homolog 2, castrate resistant prostate cancer, prostatecancer-study.com, mCRPC, efficacy, safety, pharmacokinetics, pharmacodynamics, dose escalation, dose expansion, open-label, small cell lung cancer, SCLC, follicular lymphoma, FL, relapsed, refractory
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (called Mevrometostat) for the possible treatment of Relapsed/ Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) and Follicular Lymphoma (FL). The study consists of 3 parts; Part 1 and 2 enrolled participants with SCLC, metastatic CRPC, and FL are closed for enrollment. Part 3, which is open for enrollment is seeking men who: * have Castration Resistant Prostate Cancer (CRPC) and * have previously received treatment for CRPC and have progressed from the last treatment All participants in Part 3 of this study will receive mevrometostat and/ or enzalutamide. Part 3 consists of 2 sub studies each has an assessment phase and a maintenance phase. The Part 3 DDI substudy consist of 2 cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (Combination cohort). In the assessment phase: * participants in the BE substudy will take 3 single doses of mevrometostat by mouth over 3 periods. * participants in the DDI substudy Cohort 1 (monotherapy cohort) will take mevrometostat 2 times a day and/or itraconazole 1 time a day based on a present schedule. * participants in the DDI substudy Cohort 2 (combination cohort) will take mevrometostat 2 times a day, enzalutamide 1 time a day, and/or itraconazole 1 time a day based on a present schedule. After completion of the assessment phase, participants will enter the maintenance phase where they will receive mevrometostat 2 times a day and enzalutamide 1 time a day by mouth until their cancer is no longer responding. The study will look at the experiences of participanrs receiving the study medicine. This will help see if the study medicine is safe and effective.
Detailed description
This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. The study consists of three parts (Part 1, Part 2, and Part 3) along with the Japan and China monotherapy cohorts. Part 1 and Part 2 are closed for enrollment. Part 1 tested monotherapy in 3 cohorts (Parts 1A, 1B, and 1C); Part 2 tested combination therapy in Parts 2A (dose escalation), 2B and 2C (does expansion). Part 3 consists of the Bioequivalence (BE) and drug-drug interaction (DDI) substudies and are open for enrollment. The BE substudy will test between 2 mevrometostat formulation to confirm that they work in the body the same way. The DDI substudy will evaluate the effect of a strong CYP3A4 (an enzyme in your body that breaks down/ removes drugs) inhibitor on the PK of mevrometostat; a strong CYP3A4 inhibitor may slow down the breakdown/ removal of drugs in your body. The Sponsor may choose to delay or discontinue any cohorts or substudies.
Interventions
DRUGMervometostat (PF-06821497)
Oral continuous
DRUGEnzalutamide
Oral continuous
DRUGItraconazole
Oral solution
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1 and Part 2 (Closed for enrollment). Part 3 Key Inclusion Criteria: * Histological or cytological diagnosis of castration resistant prostate cancer. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 with expected life expectancy of at least 6 months. * Adequate bone marrow, renal, and liver function Part 3 Key
Exclusion criteria
* Prior irradiation to \>25% of the bone marrow. * QTcF interval \>480 msec at screening. * Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy). * Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) * Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. * Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inducers or inhibitors * Prior enzalutamide within the last 4 weeks * DDI SUBSTUDY: * history of CHF or evidence of ventricular dysfunction * fructose intolerance * coadministration of CYP3A4 substrates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary efficacy determination as evaluated by disease specific response criteria | Through study completion, approximately 2 years past last patient first visit. | Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC. |
| Overall safety profile including laboratory abnormalities | Baseline up to approximately 2 years | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version \[4.03\]), and timing. |
| Overall safety profile including vital signs | Baseline up to approximately 2 years | Vital sign changes from baseline including blood pressure, heart rate, ECG changes. |
| Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival | Baseline until disease progression or death or through study completion (approx 2 years) | PCWG3 |
| Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) | Baseline up to 90 days | First cycle DLTs will be utilized to determine the MTD |
| Overall safety profile including adverse events | Baseline up to approximately 2 years | Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[4.03\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters: Area Under the Curve (AUC) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Single dose and multiple dose PK will be calculated as data permits |
| Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Single dose and multiple dose PK will be calculated as data permits |
| Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Single dose and multiple dose PK will be calculated as data permits |
| Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity | At specific time points from Cycle1 Day 1 to end of treatment | Questionnaire customized from PRO-CTCAE. |
| Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Singe dose and multiple dose PK will be calculated as data permits |
| Evaluate the impact of mevrometostat on patient reported outcomes. | At specific time-points from Cycle 1 Day 1 to End of Treatment visit. | Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P. |
| Evaluate time to event anti-tumor activity of mevrometostat including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type. | Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years. | Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC) |
| Evaluate overall survival | Baseline up to approximately 2 years | Median time to death proportion of patients alive at 6 months, 1 year, and 2 years. |
| Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Single dose and multiple dose PK will be calculated as data permits |
| Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) | At specific timepoints from Cycle 1 day 1 to End of Treatment visit | Single dose and multiple dose PK will be calculated as data permits |
Countries
Bulgaria, China, Japan, Poland, Russia, South Korea, Spain, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed