Clinical trial NCT00838578: Phase I/II Study of KRN330 Plus Irinotecan in Patients With Metastatic Colorectal Cancer
Official title: Phase I/II Study of KRN330 Plus Irinotecan After First-Line or Adjuvant FOLFOX/CapOx Failure in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: 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 by Site
Digestive System Diseases
Therapeutic Uses
Fluorouracil
Neoplasms
Gastrointestinal Neoplasms
Antineoplastic Agents, Phytogenic
Colorectal Neoplasms
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kirin Pharma, Inc.
First posted: 2009-02-06
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0
timeFrame: Until disease progression, death, or withdrawal post initial KRN330 treatment, assessed up to 100 months
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center, Georgetown University Hospital
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: University of Florida COllege of Medicine/Shands Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: New York
country: United States
facility: NYU Clinical Trials Office, New York University Cancer Institute
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Kyowa Hakko Kirin Pharma, Inc.
name: Michael Kurman, MD
role: STUDY_DIRECTOR
References: