Back to resultsA Study of Oral MBQ-167 in Participants With Advanced Breast Cancer
Primary Purpose
Breast Cancer, Breast Neoplasm, Breast Cancer Stage IV
Status
Recruiting
Phase
Phase 1
Locations
Puerto Rico
Study Type
Interventional
Intervention
MBQ-167
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Advanced Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer
Eligibility Criteria
Key Inclusion Criteria: 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. Key Exclusion Criteria: 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 30 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 30 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.
Sites / Locations
- FDI Clinical ResearchRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MBQ-167 oral capsule
Arm Description
A dose ranging from 10mg to 400mg BID following a standard 3+3 cohort design
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
To find the maximum tolerated dose (MTD) of MBQ-167 as a single agent administered orally, BID continuously for 21 days in participants with Advanced Breast Cancer (ABC) by evaluating for the presence or absence of dose-limiting toxicity (DLT) related to MBQ-167 administered in cohorts of participants at escalating sequential cohort dose levels.
Secondary Outcome Measures
MBQ-167 PK parameter (Cmax/min)
Maximum and minimum observed plasma concentration at steady state
MBQ-167 PK parameter (tmax)
Time to maximum plasma concentration
MBQ-167 PK parameter (t1/2)
Terminal elimination half-life
MBQ-167 PK parameter (AUC (0-t,0-24,∞))
Area under the concentration-time curve over the dosing interval time from time 0
MBQ-167 PD parameter (differential gene expression)
Observed quantitative measurement of gene expression change from baseline
MBQ-167 PK/PD parameter (minimum dose for therapeutic response)
Correlate differential gene expression change, objective response and PK parameter Cmax/min to identify a minimum dose for therapeutic response
Full Information
NCT ID
NCT06075810
First Posted
September 26, 2023
Last Updated
October 4, 2023
Sponsor
MBQ Pharma
Collaborators
United States Department of Defense
1. Study Identification
Unique Protocol Identification Number
NCT06075810
Brief Title
A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer
Official Title
A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2023 (Anticipated)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MBQ Pharma
Collaborators
United States Department of Defense
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Breast Neoplasm, Breast Cancer Stage IV
Keywords
Advanced Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open-label dose escalation following a standard 3+3 cohort design with a 21 day Dose Limiting Toxicity (DLT) evaluation
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MBQ-167 oral capsule
Arm Type
Experimental
Arm Description
A dose ranging from 10mg to 400mg BID following a standard 3+3 cohort design
Intervention Type
Drug
Intervention Name(s)
MBQ-167
Other Intervention Name(s)
Rac and Cdc42 inhibitor, Rac inhibitor, Cdc42 inhibitor, PAK inhibitor, Rac/Cdc42 inhibitor
Intervention Description
MBQ-167, an inhibitor of Rho GTPases Rac and Cdc42
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
To find the maximum tolerated dose (MTD) of MBQ-167 as a single agent administered orally, BID continuously for 21 days in participants with Advanced Breast Cancer (ABC) by evaluating for the presence or absence of dose-limiting toxicity (DLT) related to MBQ-167 administered in cohorts of participants at escalating sequential cohort dose levels.
Time Frame
21 days
Secondary Outcome Measure Information:
Title
MBQ-167 PK parameter (Cmax/min)
Description
Maximum and minimum observed plasma concentration at steady state
Time Frame
56 days
Title
MBQ-167 PK parameter (tmax)
Description
Time to maximum plasma concentration
Time Frame
56 days
Title
MBQ-167 PK parameter (t1/2)
Description
Terminal elimination half-life
Time Frame
56 days
Title
MBQ-167 PK parameter (AUC (0-t,0-24,∞))
Description
Area under the concentration-time curve over the dosing interval time from time 0
Time Frame
56 days
Title
MBQ-167 PD parameter (differential gene expression)
Description
Observed quantitative measurement of gene expression change from baseline
Time Frame
16 days
Title
MBQ-167 PK/PD parameter (minimum dose for therapeutic response)
Description
Correlate differential gene expression change, objective response and PK parameter Cmax/min to identify a minimum dose for therapeutic response
Time Frame
56 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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.
Key Exclusion Criteria:
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 30 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 30 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott Houston
Phone
(415) 404 8838
Email
scott.houston@mbqpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jose Rodriguez-Orengo, PhD
Email
jose.rodriguez@mbqpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil Sankar, MD
Organizational Affiliation
CMO, MBQ Pharma
Official's Role
Study Director
Facility Information:
Facility Name
FDI Clinical Research
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mirelis Acosta-Rivera, MD
Phone
(787) 722-1248
Email
info@fdipr.com
First Name & Middle Initial & Last Name & Degree
Michelle Echeandia, MT, MSMT
Phone
(787) 722-1248
Email
mecheandia@fdipr.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34607932
Citation
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.
Results Reference
background
PubMed Identifier
36861094
Citation
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.
Results Reference
background
PubMed Identifier
28450422
Citation
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.
Results Reference
background
PubMed Identifier
37397366
Citation
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.
Results Reference
background
PubMed Identifier
29858187
Citation
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.
Results Reference
background
PubMed Identifier
34074257
Citation
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.
Results Reference
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A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer
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