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

Chemotherapy-induced Peripheral Neuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05251727
• Other study ID #: ART-123.PN101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 24, 2022
• Est. completion date: September 2024

Study information

• Verified date: January 2024
• Source: Veloxis Pharmaceuticals
• Contact: Pamela Allton
• Phone: 984-301-2320
• Email: pal[@]veloxis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy-induced Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• thrombomodulin alfa
Weight based dose of reconstituted treatment
• Placebo
Weight based dose of reconstituted treatment

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Veloxis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Number and Percentage of Participants with Abnormal Qualitative Urinalysis Results	Qualitative summary of the following by cohort: protein, glucose, and occult blood	6 weeks
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)