A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer

Официальное название

A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer

Обзор

A Phase 1, open-label, dose-escalation clinical trial of MBQ-167 in participants with advanced Breast Cancer for whom Standard of Care (SOC) has failed or has proven intolerable.

Подробное описание

The main questions this clinical trial aims to answer are:

* What, if any, are the side effects of different dose levels in humans? * What is the maximum tolerated dose? * How does the human body process the drug? * Does the drug slow, stop or eliminate cancer in human participants?

Participants will be asked to:

* provide informed consent * be evaluated by physicians and provide laboratory specimens to determine if eligible * take MBQ-167 orally twice a day for at least 21 days * may continue dosing, if safe to do so, until not effective or other decision to stop is made * participate in multiple visits that include additional evaluations, laboratory tests and diary review until after stopping the investigational drug

Вмешательства

• Препарат MBQ-167
  MBQ-167, an inhibitor of Rho GTPases Rac and Cdc42

Первичные конечные точки

• Maximum Tolerated Dose (MTD) [Срок оценки: 21 days]

Вторичные конечные точки (6)

• MBQ-167 PK parameter (Cmax/min) [Срок оценки: 56 days]
• MBQ-167 PK parameter (tmax) [Срок оценки: 56 days]
• MBQ-167 PK parameter (t1/2) [Срок оценки: 56 days]
• MBQ-167 PK parameter (AUC (0-t,0-24,∞)) [Срок оценки: 56 days]
• MBQ-167 PD parameter (differential gene expression) [Срок оценки: 16 days]
• MBQ-167 PK/PD parameter (minimum dose for therapeutic response) [Срок оценки: 56 days]

Критерии участия

Критерии включения

• The investigator will evaluate these and other criteria to determine whether a participant can be included in this study.
• Histologically and/or cytologically confirmed advanced breast cancer which has progressed after treatment with approved therapies or for which there are no standard therapies available.
• Participants with known brain metastases may be eligible if specific conditions are met.
• Life expectancy ≥6 months, in the opinion of the investigator, after starting MBQ-167.
• Are able to swallow capsules twice daily with a meal.

Критерии исключения

• The investigator will evaluate these and other criteria to determine whether a participant should be excluded from this study.
• Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of MBQ-167.
• Females who are pregnant or breastfeeding.
• Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 28 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment.
• Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 28 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment.
• Active malignancies other than advanced breast cancer will be excluded from the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Precision Next Gen Oncology & Research Center — Beverly Hills
• Florida Cancer Specialists / Sarah Cannon Research Institute / SCRI — Sarasota
• Sarah Cannon Research Institute/SCRI — Nashville

Пуэрто-Рико · 1 центр

• FDI Clinical Research — San Juan

Публикации

• Cruz-Collazo A, Ruiz-Calderon JF, Picon H, Borrero-Garcia LD, Lopez I, Castillo-Pichardo L, Del Mar Maldonado M, Duconge J, Medina JI, Bayro MJ, Hernandez-O'Farrill E, Vlaar CP, Dharmawardhane S. Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer. Mol Cancer Ther. 2021 Dec;20(12):2420-2432. doi: 10.1158/1535-7163.MCT-21-0348. Epub 2021 Oct 4. PMID 34607932
• Medina JI, Cruz-Collazo A, Del Mar Maldonado M, Gascot TM, Borrero-Garcia LD, Cooke M, Kazanietz MG, O'Farril EH, Vlaar CP, Dharmawardhane S. Characterization of Novel Derivatives of MBQ-167, an inhibitor of the GTP-binding proteins Rac/Cdc42. Cancer Res Commun. 2022 Dec;2(12):1711-1726. doi: 10.1158/2767-9764.crc-22-0303. Epub 2022 Dec 29. PMID 36861094
• Humphries-Bickley T, Castillo-Pichardo L, Hernandez-O'Farrill E, Borrero-Garcia LD, Forestier-Roman I, Gerena Y, Blanco M, Rivera-Robles MJ, Rodriguez-Medina JR, Cubano LA, Vlaar CP, Dharmawardhane S. Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer. Mol Cancer Ther. 2017 May;16(5):805-818. doi: 10.1158/1535-7163.MCT-16-0442. PMID 28450422
• Torres-Sanchez A, Rivera-Robles M, Castillo-Pichardo L, Martinez-Ferrer M, Dorta-Estremera SM, Dharmawardhane S. Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models. Front Oncol. 2023 Jun 16;13:1152458. doi: 10.3389/fonc.2023.1152458. eCollection 2023. PMID 37397366
• Maldonado MDM, Dharmawardhane S. Targeting Rac and Cdc42 GTPases in Cancer. Cancer Res. 2018 Jun 15;78(12):3101-3111. doi: 10.1158/0008-5472.CAN-18-0619. Epub 2018 Jun 1. PMID 29858187
• Borrero-Garcia LD, Del Mar Maldonado M, Medina-Velazquez J, Troche-Torres AL, Velazquez L, Grafals-Ruiz N, Dharmawardhane S. Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer. BMC Cancer. 2021 Jun 1;21(1):652. doi: 10.1186/s12885-021-08366-7. PMID 34074257

Идентификаторы

NCT: NCT06075810 · MBQ-ABC001 · CDMRP-BC220292

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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