Phase I/II Study of KRN330 Plus Irinotecan in Patients With Metastatic Colorectal Cancer

Phase I/II Study of KRN330 Plus Irinotecan After First-Line or Adjuvant FOLFOX/CapOx Failure in Patients With Metastatic Colorectal Cancer

The primary objective of the Phase II portion of this study is to assess the efficacy of KRN330 in combination with irinotecan after first-line or adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin)/CapOx (capecitabine and oxaliplatin) treatment failure in patients with metastatic colorectal cancer.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: KRN330; Drug: Irinotecan

Detailed Description

Phase II portion is an open-label, single arm study. Based on the results of the Phase I portion, weekly KRN330 (0.5 mg/kg) and biweekly irinotecan (180 mg/m2) will be used in the Phase II portion. To be eligible for the Phase II portion, a patient will have recurred or progressed within 6 months of the last cycle of FOLFOX/CapOx +/- bevacizumab (first-line or adjuvant regimen for metastatic colorectal cancer). Patients will continue the treatment until disease progression.

Per protocol, the decision was made to terminate the study based on interim analysis results. The Response Rate in Phase II did not meet the protocol-specified RR of 15% when 0.5 mg/kg KRN330 was administered weekly in combination with irinotecan(180 mg/m2)biweekly.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Clearview Cancer Institute
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center
  • California
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2113
      • Lombardi Comprehensive Cancer Center, Georgetown University Hospital
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32610
      • University of Florida COllege of Medicine/Shands Cancer Center
    • Miami, Florida, United States, 33136
      • University of Miami - Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University - Winship Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Clinical Trials Office, New York University Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have histologically confirmed colorectal cancer that is metastatic with measurable disease.
• For the Phase II portion: Have recurred or progressed within 6 months of the last cycle of FOLFOX +/- bevacizumab first-line or adjuvant regimen for metastatic colorectal cancer. Note: Those who had initiated FOLFOX/CapOx but stopped oxaliplatin because of intolerable toxicity are also eligible.
• At least 4 weeks have elapsed since the last chemotherapy, radiotherapy, immunotherapy, or biologic therapy prior to enrollment (except at least 6 weeks in the case of nitrosourea and mitomycin).
• Have not received any other investigational agents within 4 weeks of study entry and have fully recovered from any adverse event due to prior therapy.
• At least 4 weeks have elapsed since any major surgery.
• Have ECOG performance status of 0, 1, or 2.
• Have adequate bone marrow and organ function

Exclusion Criteria:

• Have an active, uncontrolled infection.
• Have known HIV positive status.
• Have known or suspected cerebral metastasis.
• Have had a myocardial infarction (MI) or cerebrovascular accident (CVA) within the last 6 months; or meet the criteria for AHA class III or IV congestive heart failure (CHF).
• Have a medical condition requiring chronic use of high-dose corticosteroids or other chronic immunosuppressive therapy (e.g. methotrexate, azathioprine).
• Have a history of greater than or equal to Grade 2 allergic reaction or hypersensitivity following exposure to humanized or human monoclonal antibodies (but not chimeric antibodies).
• Pregnant or breastfeeding women and male or female patients who do not agree to use effective contraceptive method(s) during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KRN330 + Irinotecan; open label, single arm	Biological: KRN330; KRN330 will be dosed at 0.5 mg/kg weekly until disease progression.; Drug: Irinotecan; Irinotecan will be dosed at 180 mg/m2 biweekly until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0	Until disease progression, death, or withdrawal post initial KRN330 treatment, assessed up to 100 months

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.
• Collaborators: Kyowa Hakko Kirin Pharma, Inc.
• Investigators: Study Director: Michael Kurman, MD, Kyowa Hakko Kirin Pharma, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 4, 2009
• First Submitted That Met QC Criteria: February 5, 2009
• First Posted (Estimated): February 6, 2009

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasms; Fluorouracil; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colorectal Cancer; Antineoplastic Agents; Enzyme Inhibitors; Irinotecan; Physiological Effects of Drugs; Colorectal Neoplasms; Colonic Diseases; Pharmacologic Actions; Therapeutic Uses; Antimetabolites; Immunologic Factors; Immunosuppressive Agents; Neoplasms by Site; Antineoplastic Agents, Phytogenic; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Rectal Diseases; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; KRN330
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: KRN330-US-02