Colorectal Cancer
Conditions
Keywords
Colorectal cancer, KRAS wild type tumors
Brief summary
This study is being performed to test if the use of high dose of cetuximab in combination with irinotecan overcomes the resistance seen with standard dose of cetuximab plus irinotecan in patients with wild type KRS tumors that have advanced colon or rectal cancer
Detailed description
Cetuximab is a manufactured antibody-antibodies are proteins that can be found circulating in your blood stream. The growth of colorectal cancer may be affected by the interaction of a growth factor known as epidermal growth factor (EGF) with its receptor. Cetuximab is a antibody directed against the receptor for EGF and has been shown to turn off the activity of the receptor and to stop the growth of cancer cells in many laboratory tests. Cetuximab has been recently approved by the Food and Drug Administration in the treatment of patients with advanced colorectal cancer and who failed standard chemotherapy. Cetuximab has been shown to delay the progression of colorectal cancer when given alone in patients who have failed standard chemotherapy and when given with a chemotherapy drug called irinotecan in patients who have failed irinotecan.
Interventions
DRUGcetuximab with irinotecan
Cetuximab administered 500mg/m2 over 120 minutes Irinotecan administered Q 3 weeks, Q 2 weeks or Q week x 4 every 6 weeks depending on patients previous treatment
Sponsors
Bristol-Myers Squibb
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed colon cancer that is metastatic or unresectable * Progressed on cetuximab plus irinotecan based combination prior to enrolling on this study * Patient must have tumor tissue tested for KRAS mutation and should be confirmed to carry a wild type * ECOG less than or equal to 1 * Must have adequate organ and marrow function * Ability to understand and the willingness to sign a written informed consent document. * Presence of measurable disease defined as a lesion ≥ 2 cm by CT (or 1 cm by spiral CT). All sites of disease should be evaluated ≤ 3 weeks before treatment initiation * Patients should have failed or been deemed intolerant to other standard chemotherapy treatments such as oxaliplatin and fluoropyrimidines
Exclusion criteria
* Patients may not be receiving any other investigational agents that are not included in this study. Prior investigational anticancer agents wil not be allowed within 4 weeks prior to study treatment. Herbal medicine and vitamins wil not be considered as contraindications for enrollment on study. * Patients with known brain metastases are not eligible unless brain metastases are treated and stable on radiographic follow-up and without significant symptomatology * History of other invasive cancers with current evidence of disease * Patients should be off chemotherapy or other targeted therapies for at least 3 weeks before study treatment. Mitomycin C treatment should be at least 6 weeks before study treatment * History of allergic reactions to irinotecan * Prior severe infusion reaction to cetuximab * History of allergic reaction to tetracycline or doxycycline * Need for prior dose reduction on cetuximab secondary to grade 3 skin toxicity * Active skin toxicity of grade 2 or higher at the time of study enrollment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because the chemotherapeutic agents proposed are category D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated on this study. * Grade 2 or higher hypomagnesemia at baseline evaluation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 12-week Progression Free Survival Rate Upon Escalation of Cetuximab Dose to 500mg/m2 in Combination With Irinotecan After Progression on Standard Dose Therapy in Patients With KRS Wild Type Colorectal Cancer | 12 week |
Secondary
| Measure | Time frame |
|---|---|
| Response Rate of Cetuximab 500mg/m2/Week in Combination With Irinotecan in the Enrolled Patient Population | 18 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab With Irinotecan cetuximab with irinotecan: Cetuximab administered 500mg/m2 over 120 minutes Irinotecan administered Q 3 weeks, Q 2 weeks or Q week x 4 every 6 weeks depending on patients previous treatment | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Disease Progression | 18 |
Baseline characteristics
| Characteristic | Cetuximab With Irinotecan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 8 / 20 |
Outcome results
Primary
12-week Progression Free Survival Rate Upon Escalation of Cetuximab Dose to 500mg/m2 in Combination With Irinotecan After Progression on Standard Dose Therapy in Patients With KRS Wild Type Colorectal Cancer
Time frame: 12 week
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Irinotecan | 12-week Progression Free Survival Rate Upon Escalation of Cetuximab Dose to 500mg/m2 in Combination With Irinotecan After Progression on Standard Dose Therapy in Patients With KRS Wild Type Colorectal Cancer | 50 percentage of participants |
Secondary
Response Rate of Cetuximab 500mg/m2/Week in Combination With Irinotecan in the Enrolled Patient Population
Time frame: 18 months
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Irinotecan | Response Rate of Cetuximab 500mg/m2/Week in Combination With Irinotecan in the Enrolled Patient Population | 5 percentage of particitpants |