ME-344 and Bevacizumab in Previously Treated Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

A Phase 1b Study of the OxPhos Inhibitor ME-344 Combined With Bevacizumab in Previously Treated Metastatic Colorectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05824559
• Other study ID #: ME-344-003
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 7, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: MEI Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1b open-label, multiple dose/schedule sequential study to determine the safety and efficacy of the oxidative phosphorylation (OxPhos) pathway inhibitor ME-344 in combination with bevacizumab in subjects with recurrent mCRC.

Description:

This is a Phase 1b open-label, multiple dose/schedule sequential study to determine the safety and efficacy of the oxidative phosphorylation (OxPhos) pathway inhibitor ME-344 in combination with bevacizumab in subjects with recurrent mCRC. This study will enroll subjects with metastatic CRC, including but not limited to subjects with RAS wild-type or mutant tumors, MSI-H/pMMR, and BRAF V600E, who have progressed or demonstrated intolerability to standard approved therapies which include fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapies, cetuximab/panitumumab, PD-1 inhibitors, or BRAF inhibitors (if clinically indicated), and/or other checkpoint inhibitors. Approximately 40 subjects will be enrolled in the study, in 2 cohorts of 20 subjects each. Subjects will continue treatment with ME-344 and bevacizumab until radiological progressive disease, unacceptable AEs, withdrawal of consent, start of new anticancer therapy, or death.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years
• Histological or cytological documentation of adenocarcinoma of the colon or rectum that is metastatic (all other histological types are excluded)
• Subjects who progressed or demonstrated intolerability to prior standard approved therapies which include fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapies, cetuximab/panitumumab (if clinically indicated e.g., RAS wild-type tumors) PD-1 or BRAF inhibitors (if clinically indicated), and/or other checkpoint inhibitors in the metastatic setting.
• Previous treatment with any investigational drug or anticancer treatment must be completed >28 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Untreated brain metastases, spinal cord compression, or primary brain tumor
• Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
• Evidence of uncontrolled or unstable cardiovascular disease, myocardial infarction (within 6 months), unstable angina pectoris, congestive heart failure, serious arrhythmias requiring drug therapy
• History of CNS disease
• Bevacizumab or aflibercept therapy = 3 weeks prior to starting study treatment
• Peripheral neuropathy Grade = 2
• Uncontrolled hypertension or diabetes mellitus, active peptic ulcers, unhealed wounds, clinically significant disease or systemic infections
• Known seropositive for, or active infection with hepatitis B or C virus
• Symptomatic or uncontrolled infection with human T-cell leukemia virus
• Venous thromboembolism (unless appropriately treated and stable on anticoagulant for at least 2 weeks).

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• ME-344
ME-344 will be administered intravenously (IV)
• Bevacizumab
Bevacizumab will be administered intravenously (IV)

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	University of Southern California	Los Angeles	California
United States	Mount Sinai Miami	Miami Beach	Florida
United States	Vanderbilt -Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers University	New Brunswick	New Jersey
United States	Mt Sinai New York	New York	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
MEI Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) rate at 16 weeks	This will be measured using the Kaplan Meir (KM) method, and calculated from day of first study drug until observation of disease progression.	16 weeks
Secondary	Overall Response Rate (ORR)	This will be measure by the proportion of patients achieving complete response [CR] or partial response [PR] per RECIST v.1.1).	6 months
Secondary	Safety and tolerability of ME-344 administered in combination with bevacizumab	This will be measured by the number of participants with treatment emergent Adverse Events, with abnormal physical examination findings, abnormal vital signs, abnormal ECG QT interval and abnormal clinical laboratory results	1 year