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

Официальное название

A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF 06821497 (MEVROMETOSTAT) IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Mervometostat (PF-06821497)
  Oral continuous
• Препарат Enzalutamide
  Oral continuous
• Препарат Itraconazole
  Oral solution

Первичные конечные точки

• Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [Срок оценки: Baseline up to 90 days]
• Overall safety profile including adverse events [Срок оценки: Baseline up to approximately 2 years]
• Preliminary efficacy determination as evaluated by disease specific response criteria [Срок оценки: Through study completion, approximately 2 years past last patient first visit.]
• Overall safety profile including laboratory abnormalities [Срок оценки: Baseline up to approximately 2 years]
• Overall safety profile including vital signs [Срок оценки: Baseline up to approximately 2 years]
• Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival [Срок оценки: Baseline until disease progression or death or through study completion (approx 2 years)]

Вторичные конечные точки (10)

• 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. [Срок оценки: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.]
• Evaluate overall survival [Срок оценки: Baseline up to approximately 2 years]
• Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Area Under the Curve (AUC) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [Срок оценки: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Evaluate the impact of mevrometostat on patient reported outcomes. [Срок оценки: At specific time-points from Cycle 1 Day 1 to End of Treatment visit.]
• Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity [Срок оценки: At specific time points from Cycle1 Day 1 to end of treatment]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 44 центра

• Banner-University Medical Center Tucson — Tucson
• The University of Arizona Cancer Center-North Campus — Tucson
• The University of Arizona Cancer Center — Tucson
• Arizona Urology Specialists, PLLC — Tucson
• Pacific Cancer Medical Center INC — Anaheim
• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• City of Hope Investigational Drug Services (IDS) — Duarte
• Norwalk Hospital — Norwalk
• … и ещё 36 центров

Испания · 12 центров

• Institut Català d´Oncología (ICO)-H. Durán i Reynals — L'Hospitalet de Llobregat
• Consorcio Hospitalario Provincial de Castellon — Castellon
• Hospital Quironsalud Madrid — Pozuelo de Alarcón
• Hospital Quironsalud Barcelona — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid
• H.U. Fundación Jiménez Díaz — Madrid
• … и ещё 4 центра

Россия · 9 центров

• Private Medical Institution "Euromedservice" — Pushkin
• LLC "Neyro-klinika" — Moscow
• Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department — Moscow
• SBHI of Moscow City Clinical Hospital — Moscow
• Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary" — Omsk
• Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov — Saint Petersburg
• Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N — Saint Petersburg
• Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispens — Saint Petersburg
• … и ещё 1 центр

Китай · 6 центров

• The First Affiliated Hospital of Guangzhou Medical University — Гуанчжоу
• Hunan Cancer Hospital — Чанша
• Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School — Нанкин
• Zhongda Hospital Southeast University — Нанкин
• West China Hospital, Sichuan University — Чэнду
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

South Korea · 5 центров

• Seoul National University Bundang Hospital — Seongnam
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Ewha Womans University Mokdong Hospital — Seoul
• Chungnam national university hospital — Daejeon

Польша · 4 центра

• Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie — Koszalin
• Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o. — Krakow
• Centrum Medyczne MEDYK — Rzeszów
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w W — Warsaw

Болгария · 1 центр

• Specialized Hospital for Active Treatment of Oncology - Haskovo — Haskovo

Япония · 1 центр

• National Cancer Center Hospital East — Kashiwa

Идентификаторы

NCT: NCT03460977 · C2321001 · EZH2 · 2023-509179-18-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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