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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: KRN330
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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