Colorectal Cancer
Conditions
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
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.
Interventions
BIOLOGICALKRN330
KRN330 will be dosed at 0.5 mg/kg weekly until disease progression.
DRUGIrinotecan
Irinotecan will be dosed at 180 mg/m2 biweekly until disease progression.
Sponsors
Kyowa Hakko Kirin Pharma, Inc.
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KRN330 + Irinotecan open label, single arm | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | KRN330 + Irinotecan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age, Continuous | 59.83 years STANDARD_DEVIATION 10.185 |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 7 / 7 | 42 / 44 |
| serious Total, serious adverse events | 6 / 12 | 2 / 7 | 17 / 44 |
Outcome results
Primary
Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0
Time frame: Until disease progression, death, or withdrawal post initial KRN330 treatment, assessed up to 100 months
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A: KRN330 Biweekly + Irinotecan Biweekly | Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0 | 12 participants |
| Regimen B: KRN330 Weekly + Irinotecan Biweekly | Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0 | 7 participants |
| PH 2 Treatment: KRN330 Wkly + IRI Biwkly | Number of Participants With Serious and Other (Non-Serious) Adverse Events According to the CTCAE v.3.0 | 44 participants |