A Study of Mevrometostat for Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

Clinicaltrials.gov ID: NCT03460977

Status RECRUITING

Phase PHASE1

Age ≥ 18 Years

Enrollments 433

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)

Drugs

Mervometostat (PF-06821497), Enzalutamide

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 treatmentAll 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.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 will take mevrometostat 2 times a day, with or without 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 studywill 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.

Locations

22 locations Found with status Recruiting

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Status

RECRUITING

Central Contacts

Pfizer CT.gov Call Center
1-800-718-1021
[email protected]

Study Director

Pfizer CT.gov Call Center

Eligibility 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

Study Plan

Dose Escalation (Part 1A)

EXPERIMENTAL

Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous

Dose Escalation (Part 1B)

EXPERIMENTAL

Participants with FL will receive mevrometostat at escalating dose levels

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous

Dose Escalation (Part 1C)

EXPERIMENTAL

Participants with mCRPC will receive PF-06821497 at escalating dose levels.

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous

Dose Escalation (Part 2A)

EXPERIMENTAL

Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous
DRUG:
Enzalutamide
Description:
Oral continuous

Dose Expansion (Part 2B)

EXPERIMENTAL

Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous
DRUG:
Enzalutamide
Description:
Oral continuous

Japan Cohort

EXPERIMENTAL

Participants with CRPC will receive mevrometostat at one or two doses

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous

China cohort

EXPERIMENTAL

Participants will receive mevrometostat at one or two doses

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous

Dose Expansion (Part 2C)

EXPERIMENTAL

Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous
DRUG:
Enzalutamide
Description:
Oral continuous

BE Substudy

EXPERIMENTAL

In the assessment phase, each enrolled participant will receive single doses of the 2 different mevrometostat formulations in 3 periods with alternating dosing and washout between each dose. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous
DRUG:
Enzalutamide
Description:
Oral continuous

DDI Substudy

EXPERIMENTAL

In the assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.

DRUG:
Mervometostat (PF-06821497)
Description:
Oral continuous
DRUG:
Enzalutamide
Description:
Oral continuous

Outcome Measures

Primary Outcome Measures

Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)

Time Frame: Baseline up to 90 days

Overall safety profile including adverse events

Time Frame: Baseline up to approximately 2 years

Preliminary efficacy determination as evaluated by disease specific response criteria

Time Frame: Through study completion, approximately 2 years past last patient first visit.

Overall safety profile including laboratory abnormalities

Time Frame: Baseline up to approximately 2 years

Overall safety profile including vital signs

Time Frame: Baseline up to approximately 2 years

Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival

Time Frame: Baseline until disease progression or death or through study completion (approx 2 years)

Secondary Outcome Measures

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.

Time Frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.