Assess Safety and Tolerability of ART-123 + FOLFOX + Bevacizumab in Metastatic Colorectal Cancer Patients
- Conditions
- Chemotherapy-induced Peripheral Neuropathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT05251727
- Lead Sponsor
- Veloxis Pharmaceuticals
- Brief Summary
To evaluate the safety and tolerability of ART-123 in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab
- Detailed Description
To compare the safety and tolerability of ART-123 to placebo in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 77
- 18 years of age or older
- Metastatic colorectal cancer; pathologically confirmed adenocarcinoma of the colon or rectum
- ECOG performance status of 0 or 1
- The most recent laboratory findings (including for liver and kidney) within 14 days prior to randomization remain within acceptable ranges Willingness of the patient and the sexual partner to use a highly effective contraceptive method during the course of the study
- Able to sufficiently understand the clinical study and give written informed consent
- History of major hemorrhage
- High risk of hemorrhage
- History of other malignancies
- Active ulcer
- Patients using anti-coagulants and fibrinolytic drugs
- Active Hepatitis B, or known HBs antigen positive
- Prior treatment history with thrombomodulin alfa
- Administration of another investigational medicinal product within 30 days prior to randomization
- Patient is pregnant (positive urine human chorionic gonadotropin) or breastfeeding or intends to get pregnant during the Treatment period
- Patients otherwise deemed as inappropriate to participate in the study by the Investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lowest Dose thrombomodulin alfa Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab) Low Dose thrombomodulin alfa Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)" Medium Dose thrombomodulin alfa Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)" High Dose thrombomodulin alfa Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)" Placebo Placebo Lyophilized placebo reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)" Highest Dose thrombomodulin alfa Lyophilized ART-123 reconstituted with sterile water for injection and administered by intravenous infusion over approximately 30 minutes prior to chemotherapy on Day 1 of cycle (for up to 3 cycles including bevacizumab)"
- Primary Outcome Measures
Name Time Method Number and Percentage of Participants with Serious TEAEs From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks Number and percentage of participants experiencing one or more serious adverse events which occurred or worsened in severity after the start of the first dose of IMP
Number and Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) From start of first IMP dose (Cycle 1, Day 1) through End of Treatment (EOT) visit; planned for 6 weeks Number and percentage of participants experiencing one or more adverse events which occurred or worsened in severity after the start of the first dose of investigational medicinal product (IMP)
Number and Percentage of Participants with Bleeding Events From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks Number and percentage of participants experiencing bleeding events
Number and Percentage of Participants with Serious Bleeding Events From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks Number and percentage of participants with bleeding events that represent serious adverse events
Number and Percentage of Participants with Abnormal Serum Chemistry Results 6 weeks Descriptive statistics will summarize the following by cohort: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, lactate dehydrogenase, total bilirubin, total protein, albumin, blood urea nitrogen, creatinine, glucose, and electrolytes (sodium, potassium, chloride)
Number and Percentage of Participants with Abnormal Coagulation Panel Results 6 weeks Descriptive statistics will summarize the following by cohort: international normalized ratio (INR), activated partial thromboplastin time (APTT)
Number and Percentage of Participants with Abnormal Qualitative Urinalysis Results 6 weeks Qualitative summary of the following by cohort: protein, glucose, and occult blood
Number and Percentage of Participants with TEAEs Leading to Death From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks Number and percentage of participants with TEAEs that resulted in death
Number and Percentage of Participants with TEAEs Leading to IMP Discontinuation From start of first IMP dose (Cycle 1, Day 1) through planned third IMP dose; planned for 4 weeks Number and percentage of participants with TEAEs that lead to discontinuation of IMP
Number and Percentage of Participants with Dose Limiting Toxicity (DLT) From start of first IMP dose (Cycle 1, Day 1) until the start of the third IMP dose; planned for 4 weeks Number and percentage of participants experiencing DLT
Number and Percentage of Participants with Abnormal Complete Blood Count (CBC) Results 6 weeks Descriptive statistics will summarize the following by cohort: red blood cell count, hemoglobin, hematocrit, white blood cell count, white blood cell differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count
Number and Percentage of Participants with Abnormal Vital Signs 6 weeks Descriptive statistics will summarize the following by cohort: body temperature, pulse, and blood pressure
Number and Percentage of Participants with Anti-ART-123 Antibodies 6 weeks Number and Percentage of Participants with detectable anti-ART-123 antibodies; samples testing positive for anti-ART-123 antibodies will be tested for the presence of neutralizing antibodies
- Secondary Outcome Measures
Name Time Method Plasma Concentrations of Thrombomodulin Cycle 1, Day 1 (each cycle is 14 days) Plasma concentrations of thrombomodulin associated with Cycle 1 dosing (each cycle is 14 days)
Plasma Concentrations of 5-fluorouracil (5-FU) Cycle 1, Day 1 (each cycle is 14 days) Plasma concentrations of 5-FU associated with Cycle 1 dosing (each cycle is 14 days)
Plasma Concentrations of Oxaliplatin Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days) Plasma concentrations of oxaliplatin associated with Cycle 1 and Cycle 3 dosing (each cycle is 14 days)
Serum Concentrations of Bevacizumab Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days) Serum concentrations of bevacizumab associated with Cycle 1 and Cycle 3 dosing (each cycle is 14 days)
Trial Locations
- Locations (32)
UCLA Dept. of Medicine - Hematology/Oncology
🇺🇸Los Angeles, California, United States
Site #114
🇺🇸Houston, Texas, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
Kitakyushubyoin Kitakyusyu General Hospital
🇯🇵Kitakyushu-shi, Japan
American Oncology Partners, P.A.
🇺🇸Bethesda, Maryland, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
Mid-Florida Hematology & Oncology Centers
🇺🇸Orange City, Florida, United States
Eastern Connecticut Hematology & Oncology Associates
🇺🇸Norwich, Connecticut, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
MultiCare Regional Cancer Center
🇺🇸Tacoma, Washington, United States
NHO Osaka National Hospital
🇯🇵Osaka-shi, Japan
NHO Kyushu Cancer Center
🇯🇵Fukuoka-shi, Japan
Horizon Oncology Research, Inc.
🇺🇸Lafayette, Indiana, United States
Kurashiki Central Hospital
🇯🇵Kurashiki-shi, Okyama, Japan
Kagawa University Hospital
🇯🇵Kita-gun, Japan
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Nashville Oncology Associates, PC
🇺🇸Nashville, Tennessee, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Kumpukai Sano Hospital
🇯🇵Kobe-shi, Japan
Gifu University Hospital
🇯🇵Gifu-shi, Japan
NHO Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Yokohama City University Medical Center
🇯🇵Yokohama-shi, Kanagawa-ken, Japan
Kochi Medical School Hospital
🇯🇵Nankoku-shi, Japan
Osaka General Medical Center
🇯🇵Osaka-shi, Japan
Shizuoka Cancer Center
🇯🇵Sunto-gun, Japan
Site #115
🇺🇸Hackensack, New Jersey, United States
Site #120
🇺🇸Dallas, Texas, United States
Tonan Hospital
🇯🇵Sapporo-shi, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-shi, Japan