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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT00838578
First received: February 4, 2009
Last updated: October 10, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: KRN330
Drug: Irinotecan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of KRN330 Plus Irinotecan After First-Line or Adjuvant FOLFOX/CapOx Failure in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Kyowa Hakko Kirin Pharma, Inc.:

Primary Outcome Measures:
  • Response rate and progression-free survival [ Time Frame: Until disease progression post initial KRN330 treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the efficacy and the safety of KRN330 plus irinotecan, obtain information on the KRN330 PK profile and determine the degree of immunogenicity. [ Time Frame: Until disease progression after initial KRN330 treatment ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: March 2009
Study Completion Date: October 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KRN330 + Irinotecan
open label, single arm
Biological: KRN330
KRN330 will be dosed at 0.5 mg/kg weekly until disease progression.
Other Name: KRN330
Drug: Irinotecan
Irinotecan will be dosed at 180 mg/m2 biweekly until disease progression.
Other Name: 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. The efficacy analysis,based on the intent-to-treat population (44 subjects) was shown to be 4.5%.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838578

Locations
United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, Arizona
Arizona Clinical Research Center
Tucson, Arizona, United States, 85715
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, District of Columbia
Lombardi Comprehensive Cancer Center, Georgetown University Hospital
Washington, District of Columbia, United States, 20007-2113
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33916
University of Florida COllege of Medicine/Shands Cancer Center
Gainesville, Florida, United States, 32610
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Emory University - Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
United States, New York
NYU Clinical Trials Office, New York University Cancer Institute
New York, New York, United States, 10016
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Kyowa Hakko Kirin Pharma, Inc.
Investigators
Study Director: Michael Kurman, MD Kyowa Hakko Kirin Pharma, Inc.
  More Information

No publications provided

Responsible Party: Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier: NCT00838578     History of Changes
Other Study ID Numbers: KRN330-US-02
Study First Received: February 4, 2009
Last Updated: October 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Kyowa Hakko Kirin Pharma, Inc.:
KRN330
Colorectal Cancer
Antimetabolites
Antimetabolites, Antineoplastic
Digestive System Neoplasms
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Physiological Effects of Drugs
Colonic Diseases
Irinotecan
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Rectal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Fluorouracil
Gastrointestinal Neoplasms
Antineoplastic Agents, Phytogenic
Colorectal Neoplasms

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014