- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05070104
CPI-613 (Devimistat) in Combination With Modified FOLFIRINOX Plus Bevacizumab in Patients With Metastatic Colorectal Cancer
Phase I Study of the First-In-Class Agent CPI-613 (Devimistat) in Combination With Modified FOLFIRINOX Plus Bevacizumab in Patients With Metastatic Colorectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 1
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Written informed consent in accordance with federal, local, and institutional guidelines
- Patients must have histologically/pathologically confirmed colorectal adenocarcinoma with measurable disease by RECIST 1.1 criteria
- Patients must have had no prior chemotherapy for metastatic disease with fluoropyrimidine based chemotherapy with oxaliplatin or irinotecan
- Patients with prior adjuvant chemotherapy are allowed, as long as a minimum of 6 months have passed between the completion of adjuvant therapy and the start of the study medication
- Age >18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Radiographic evidence of metastatic disease
At the time of study entry:
absolute neutrophil count must be ≥ 1000/mm3, hemoglobin ≥ 9 gm/dL, and platelet count ≥ 100,000/mm3 There must be evidence of adequate hepatic and renal function. Bilirubin must be ≤ 1.5 x upper limit of normal (ULN) for the lab unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin Alkaline phosphatase must be ≤ 3 x ULN for the lab AST and ALT must be ≤ 5 x ULN for the lab Serum creatinine ≤ 1.5 x ULN for the lab Note: For patients with liver metastases, non-fasting bilirubin 1.5 x ULN to 3 x ULN of the institution's normal range are acceptable.
- Both male and female patients with childbearing potential must agree to use adequatecontraception throughout the study and for 9 months after last dose of mFOLFIRINOX, bevacizumab or CPI-613 (devimistat)
- Patients without liver metastasis are eligible if they have ALT and AST ≤ 3.0 x ULN
Exclusion Criteria:
- Diagnosis of anal or small bowel carcinoma
- Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid
- Patients with tumors that are MSI-high/dMMR
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days ofreceiving study therapy
- Active infection or chronic infection requiring systemic therapy
- Known history of human immunodeficiency virus (HIV) or acquired immunodeficiencyrelated (AIDS) illnesses with CD4 count < 250 cells/mm3
Any of the following cardiac conditions:
Documented NYHA Class III or IV congestive heart failure, Myocardial infarction within 6 months prior to study entry, Unstable angina within 6 months prior to study entry, Symptomatic arrhythmia
Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 12 months prior to study entry.
Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, and basal cell and squamous cell carcinoma of the skin
- Psychiatric or addictive disorders or other conditions that in the opinion of the investigator would preclude the patient from meeting the study requirements or interfere with interpretation of study results
- Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of drug oralcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer. Patients must have neuropathy grade 1 or less
- Pregnancy or lactation at the time of study entry
- Use of any investigational agent within 4 weeks prior to the first dose study therapy
Patients with the following conditions:
Uncontrolled hypertension (defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 100 mm Hg) Bleeding diatheses or hemorrhage within 6 months prior of study enrollment Gastrointestinal perforation or fistulas History of thromboembolic events Reversible Posterior Leukoencephalopathy Syndrome (RPLS), Proteinuria > 1gr/24 hours
- Patients with current serious, non-healing wound, ulcer and baseline peripheral neuropathy of grade 2 or greater, hypersensitivity reaction to 5-FU, oxaliplatin or other platinum-based drugs, or irinotecan if it was previously administered in the adjuvant setting
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single Arm
CPI-613 mFFX Bevacizumab
|
250-1000mg/m2 -14 day cycle
Other Names:
Irinotecan: 150mg/m2 IV over 90 min-14 day cycle Leucovorin: 400mg/m2 IV over 2hrs with Irinotecan-14 day cycle Oxaliplatin: 85mg/m2 IV over 2hrs-14 day cycle 5FU: 2400mg/m2 IV over 46-48 hrs-14 day cycle
5mg/kg IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability
Time Frame: 3-6 months
|
Number of patients with Dose-limiting toxicities (DLT) will be assessed in order to be able to establish safety and tolerability for the combination of CPI-613, mFFX with bevacizumab therapy.
Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).
|
3-6 months
|
Safety and tolerability
Time Frame: 3-6 months
|
Dose-limiting toxicities assessed in order to be able to establish safety and tolerability for the combination of CPI-613, mFFX with bevacizumab therapy.
Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).
|
3-6 months
|
Recommended Phase 2 Dose
Time Frame: 3-6 months
|
Determine recommended phase 2 dose (RP2D) of CPI-613 (devimistat) (MTD) in combination with mFOLFIRINOX plus bevacizumab
|
3-6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: 3-12 months
|
It is defined as the proportion of patients who achieve complete response or partial response during or following study treatment
|
3-12 months
|
Overall Survival
Time Frame: 3-12 months
|
Defines as the time from enrollment to the date of death due to any cause.
|
3-12 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- ACHIEVE613
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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