Study of ONO-4578 and XELOX/FOLFOX Plus Bevacizumab in Colorectal Cancer

ONO-4578 Phase I Study An Open-label, Uncontrolled Study of First-line Combination Therapy of ONO-4578 and ONO-4538 With Standard Therapy XELOX Plus Bevacizumab or FOLFOX Plus Bevacizumab in Patients With Unresectable, Advanced or Recurrent Colorectal Cancer

To evaluate the tolerability and safety of combination of ONO-4578 and ONO-4538 and the standard of care XELOX + bevacizumab or the safety of combination of ONO-4578 and ONO-4538 and the standard of care FOLFOX + bevacizumab as first-line therapy in patients with unresectable, advanced, or recurrent colorectal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Drug: ONO-4538; Drug: ONO-4578; Drug: Calcium Levofolinate Hydrateb

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan
      • National Cancer Center Hospital East
  • Hyogo
    • Kobe-shi, Hyogo, Japan
      • Kobe City Hospital Organization Kobe City Medical Center General Hospital
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan
      • Kanagawa Cancer Center
  • Kitaadati-gun, Saitama
    • Ina, Kitaadati-gun, Saitama, Japan
      • Saitama Cancer Center
  • Osaka
    • Osaka-shi, Osaka, Japan
      • NHO Osaka National Hospital
    • Osaka-shi, Osaka, Japan
      • Osaka General Medical Center
    • Takatsuki-shi, Osaka, Japan
      • Osaka Medical and Pharmaceutical University Hospital
  • Saitama
    • Hidaka-shi, Saitama, Japan
      • Saitama Medical University International Medical Center
  • Tokyo
    • Koto-Ku, Tokyo, Japan
      • Cancer Institute Hospital of JFCR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Unresectable colorectal cancer
• Life expectancy of at least 3 months
• Patients with ECOG performance status 0 or 1

Exclusion Criteria:

• Patients with severe complication
• Patients are unable to swallow oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONO-4578+ONO-4538+XELOX plus bevacizumab	Drug: Oxaliplatin; Specified dose on specified days; Other Names: ELPLAT; Drug: Bevacizumab; Specified dose on specified days; Other Names: AVASTIN; Drug: Capecitabine; Specified dose on specified days; Other Names: XELODA; Drug: ONO-4538; Specified dose on specified days; Other Names: Nivolumab; Drug: ONO-4578; Specified dose on specified days
Experimental: ONO-4578+ONO-4538+FOLFOX plus bevacizumab	Drug: Fluorouracil; Specified dose on specified days; Other Names: 5-FU; Drug: Oxaliplatin; Specified dose on specified days; Other Names: ELPLAT; Drug: Bevacizumab; Specified dose on specified days; Other Names: AVASTIN; Drug: ONO-4538; Specified dose on specified days; Other Names: Nivolumab; Drug: ONO-4578; Specified dose on specified days; Drug: Calcium Levofolinate Hydrateb; Specified dose on specified days; Other Names: ISOVORIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of AEs and SAEs	up to 3years
Incidence and severity of clinical laboratory abnormalities	up to 3years
12-lead electrocardiography (Heart rate)	up to 3years
12-lead electrocardiography (PR interval)	up to 3years
12-lead electrocardiography (RR interval)	up to 3years
12-lead electrocardiography (QRS width)	up to 3years
12-lead electrocardiography (QT interval)	up to 3years
Chest X-ray test	up to 3years
ECOG performance status	up to 3years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	up to 3years
Objective response rate (ORR)	up to 3years
Disease control rate (DCR)	up to 3years
Progression-free survival (PFS)	up to 3years
Duration of response (DOR)	up to 3years
Time to response (TTR)	up to 3years
Best oveall response (BOR)	up to 3years
Percentage of change in the sum of tumor diameters of target lesions	up to 3years
Maximum percent change in the sum diameters of the target lesions	up to 3years
Time course of tumor markers	up to 3years
Plasma ONO-4578 concentration	up to 3years
Serum ONO-4538 concentration	up to 3years
Anti-ONO-4538 antibody	up to 3years

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Nivolumab; Bevacizumab; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: ONO-4578-02

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