Assess Safety and Tolerability of ART-123 + FOLFOX + Bevacizumab in Metastatic Colorectal Cancer Patients

Double-blind, Placebo-controlled, Randomized, Dose-escalating, Multi-center, Phase 1 Study to Assess the Safety and Tolerability of ART-123 With Leucovorin/5-fluorouracil/Oxaliplatin and Bevacizumab in Metastatic Colorectal Cancer Patients

To evaluate the safety and tolerability of ART-123 in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab

Study Overview

• Status: Terminated
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Drug: thrombomodulin alfa; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Japan
    • Nho Kyushu Cancer Center
  • Gifu-shi, Japan
    • Gifu University Hospital
  • Kita-gun, Japan
    • Kagawa University Hospital
  • Kitakyushu-shi, Japan
    • Kitakyushubyoin Kitakyusyu General Hospital
  • Kobe-shi, Japan
    • Kumpukai Sano Hospital
  • Matsuyama-shi, Japan
    • NHO Shikoku Cancer Center
  • Nankoku-shi, Japan
    • Kochi Medical School Hospital
  • Osaka-shi, Japan
    • NHO Osaka National Hospital
  • Osaka-shi, Japan
    • Osaka General Medical Center
  • Sapporo-shi, Japan
    • Tonan Hospital
  • Sunto-gun, Japan
    • Shizuoka Cancer Center
  • Tsukuba-shi, Japan
    • University of Tsukuba Hospital
  • Kanagawa-ken
    • Yokohama-shi, Kanagawa-ken, Japan, 232-0024
      • Yokohama City University Medical Center
  • Okyama
    • Kurashiki-shi, Okyama, Japan, 710-8602
      • Kurashiki Central Hospital
• United States
  • California
    • Beverly Hills, California, United States, 90210
      • Beverly Hills Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA Dept. of Medicine - Hematology/Oncology
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology & Oncology Associates
  • Florida
    • Orange City, Florida, United States, 32763
      • Mid-Florida Hematology & Oncology Centers
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Montana
    • Billings, Montana, United States, 59101
      • St. Vincent Frontier Cancer Center
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Site #115
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville Oncology Associates, PC
  • Texas
    • Dallas, Texas, United States, 75230
      • Site #120
    • Houston, Texas, United States, 77024
      • Site #114
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lowest Dose; 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)	Drug: thrombomodulin alfa; Weight based dose of reconstituted treatment; Other Names: ART-123
Experimental: Low Dose; 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)"	Drug: thrombomodulin alfa; Weight based dose of reconstituted treatment; Other Names: ART-123
Experimental: Medium Dose; 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)"	Drug: thrombomodulin alfa; Weight based dose of reconstituted treatment; Other Names: ART-123
Experimental: High Dose; 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)"	Drug: thrombomodulin alfa; Weight based dose of reconstituted treatment; Other Names: ART-123
Experimental: Highest Dose; 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)"	Drug: thrombomodulin alfa; Weight based dose of reconstituted treatment; Other Names: ART-123
Placebo Comparator: 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)"	Drug: Placebo; Weight based dose of reconstituted treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)	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)	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 with Serious TEAEs	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	From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and Percentage of Participants with TEAEs Leading to Death	Number and percentage of participants with TEAEs that resulted in 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 Leading to IMP Discontinuation	Number and percentage of participants with TEAEs that lead to discontinuation of IMP	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 Bleeding Events	Number and percentage of participants experiencing 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 Serious Bleeding Events	Number and percentage of participants with bleeding events that represent serious adverse events	From start of first IMP dose (Cycle 1, Day 1) through EOT visit; planned for 6 weeks
Number and Percentage of Participants with Dose Limiting Toxicity (DLT)	Number and percentage of participants experiencing 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 with Abnormal Complete Blood Count (CBC) Results	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	6 weeks
Number and Percentage of Participants with Abnormal Serum Chemistry Results	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)	6 weeks
Number and Percentage of Participants with Abnormal Coagulation Panel Results	Descriptive statistics will summarize the following by cohort: international normalized ratio (INR), activated partial thromboplastin time (APTT)	6 weeks
Number and Percentage of Participants with Abnormal Qualitative Urinalysis Results	Qualitative summary of the following by cohort: protein, glucose, and occult blood	6 weeks
Number and Percentage of Participants with Abnormal Vital Signs	Descriptive statistics will summarize the following by cohort: body temperature, pulse, and blood pressure	6 weeks
Number and Percentage of Participants with Anti-ART-123 Antibodies	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	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Thrombomodulin	Plasma concentrations of thrombomodulin associated with Cycle 1 dosing (each cycle is 14 days)	Cycle 1, Day 1 (each cycle is 14 days)
Plasma Concentrations of 5-fluorouracil (5-FU)	Plasma concentrations of 5-FU associated with Cycle 1 dosing (each cycle is 14 days)	Cycle 1, Day 1 (each cycle is 14 days)
Plasma Concentrations of Oxaliplatin	Plasma concentrations of oxaliplatin associated with Cycle 1 and Cycle 3 dosing (each cycle is 14 days)	Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days)
Serum Concentrations of Bevacizumab	Serum concentrations of bevacizumab associated with Cycle 1 and Cycle 3 dosing (each cycle is 14 days)	Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days)

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Investigators: Study Director: Libbie McKenzie, MD FASN, Veloxis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Actual): June 5, 2024
• Study Completion (Actual): June 5, 2024

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: ART-123.PN101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No