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

NCT05251727 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ART-123.PN101
• Study Type: interventional
• Target: 77
• Locations: 2 countries
• Sites: 32

Brief Summary

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

Conditions

Chemotherapy-induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (4)

• Plasma Concentrations of Thrombomodulin

  Cycle 1, Day 1 (each cycle is 14 days)

• Plasma Concentrations of 5-fluorouracil (5-FU)

  Cycle 1, Day 1 (each cycle is 14 days)

• Plasma Concentrations of Oxaliplatin

  Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days)

• Serum Concentrations of Bevacizumab

  Cycle 1, Day 1 and Cycle 3, Day 1 (each cycle is 14 days)

Study Arms (6)

Lowest Dose

EXPERIMENTAL

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

Low Dose

EXPERIMENTAL

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

Medium Dose

EXPERIMENTAL

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

High Dose

EXPERIMENTAL

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

Highest Dose

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

thrombomodulin alfa DRUG

Weight based dose of reconstituted treatment

Also known as: ART-123

High Dose; Highest Dose; Low Dose; Lowest Dose; Medium Dose

Placebo DRUG

Weight based dose of reconstituted treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Veloxis Pharmaceuticals: lead

Study Sites (32)

Beverly Hills Cancer Center

Beverly Hills, California, 90210, United States

Location

UCLA Dept. of Medicine - Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Eastern Connecticut Hematology & Oncology Associates

Norwich, Connecticut, 06360, United States

Location

Mid-Florida Hematology & Oncology Centers

Orange City, Florida, 32763, United States

Location

Horizon Oncology Research, Inc.

Lafayette, Indiana, 47905, United States

Location

American Oncology Partners, P.A.

Bethesda, Maryland, 20817, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59101, United States

Location

Englewood Hospital and Medical Center

Englewood, New Jersey, 07631, United States

Location

Site #115

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Nashville Oncology Associates, PC

Nashville, Tennessee, 37203, United States

Location

Site #120

Dallas, Texas, 75230, United States

Location

Site #114

Houston, Texas, 77024, United States

Location

MultiCare Regional Cancer Center

Tacoma, Washington, 98405, United States

Location

Yokohama City University Medical Center

Yokohama, Kanagawa, 232-0024, Japan

Location

Kurashiki Central Hospital

Kurashiki-shi, Okyama, 710-8602, Japan

Location

NHO Kyushu Cancer Center

Fukuoka, Japan

Location

Gifu University Hospital

Gifu, Japan

Location

Kagawa University Hospital

Kita-gun, Japan

Location

Kitakyushubyoin Kitakyusyu General Hospital

Kitakyushu-shi, Japan

Location

Kumpukai Sano Hospital

Kobe, Japan

Location

NHO Shikoku Cancer Center

Matsuyama, Japan

Location

Kochi Medical School Hospital

Nankoku-shi, Japan

Location

NHO Osaka National Hospital

Osaka, Japan

Location

Osaka General Medical Center

Osaka, Japan

Location

Tonan Hospital

Sapporo, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Japan

Location

University of Tsukuba Hospital

Tsukuba, Japan

Location

MeSH Terms

Interventions

ART123

Study Officials

• Libbie McKenzie, MD FASN

  Veloxis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: February 23, 2022
• Study Start: March 24, 2022
• Primary Completion: June 5, 2024
• Study Completion: June 5, 2024
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); JP (14)