Metastatic Colorectal Cancer
Conditions
Keywords
Colon, Cancer, Metastatic, Colorectal
Brief summary
The purpose of this study is to see if alternating chemotherapy with erlotinib increases tumor shrinkage in people with metastatic colorectal cancer. The investigator will also be studying the side effects (good and bad) of alternating chemotherapy with erlotinib on metastatic colorectal cancer.
Interventions
DRUGErlotinib
Erlotinib oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. In addition to the active ingredient, erlotinib contains lactose (hydrous), microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, and magnesium stearate. Tablets containing 25 mg, 100 mg, and 150 mg of erlotinib are available. Each bottle will contain 30 tablets, a quantity sufficient for 4 consecutive weeks of dosing, with overage.
DRUGFluorouracil
Antimetabolite used as a chemotherapy. Administered intravenously as a bolus injection at 400mg/m2 on Day 1 followed by 2400 mg/m2 continuously over 46 hours.
DRUGLeucovorin
Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.
DRUGOxaliplatin
Platinum-based antineoplastic chemotherapy agent given intravenously at 85 mg/m2.
DRUGIrinotecan
Chemotherapy agent given intravenously at 180 mg/m2.
Sponsors
Genentech, Inc.
OSI Pharmaceuticals
OHSU Knight Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients must fulfill all of the following criteria to be eligible for study entry: * Age 18-80 * Able to provide informed consent * Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum * Documented progression on prior first-line oxaliplatin-based or irinotecan-based regimen for metastatic colorectal cancer * Radiographically measurable disease with at least one bidimensionally measurable lesion of \> 1 cm * Prior first-line regimen must have been completed at least 4 weeks prior to study treatment * Use of biologic agents with first-line chemotherapy permitted * Previous adjuvant regimens must have been greater than 6 months before inclusion * Adequate organ function including bone marrow, liver and renal function as defined by the following values: absolute neutrophil count \> 1500/microliter; Hgb \> 9 g/dL; platelets \> 90,000/microliter; International Normalized Ratio \< 1.8 (unless in therapeutic range if taking warfarin or other warfarin-derivative anticoagulants and are being monitored regularly for changes in prothrombin time or International Normalized Ratio); bilirubin \< 2 times the Upper Limit of Normal; alkaline phosphatase \< 3 times the Upper Limit of Normal; aspartate aminotransferase/alanine aminotransferase \< 5 times the Upper Limit of Normal; serum creatinine \< 1.5 times the Upper Limit of Normal * Eastern Cooperative Oncology Group status \< 2
Exclusion criteria
Patients meeting any of the following criteria are ineligible for study entry: * Prior second-line chemotherapy regimens for colorectal cancer * Prior treatment with erlotinib or gefitinib * Central Nervous System metastasis * Second malignancies less than 5 years prior to enrollment. Completely resected basal or squamous cell carcinoma of the skin is allowed. * Untreated/unresolved bowel obstruction * Inability to take oral mediations * HIV positive * Pregnancy * Other uncontrolled medical illnesses * Current diarrhea \> grade 2 * Symptomatic angina or uncontrolled congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates of Radiographically Measurable Disease | Disease response assessed after every 2 Treatment Cycles, or around 8 weeks. | The primary outcome measure will be the response rates of radiographically measurable disease. Response rate of disease will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Second-line Progression Free Survival | Upon completion of follow-up, for an average of 99 days following the initiation of study treatment. | Time to disease progression from start of second-line experimental regimen. Disease progression will be measured per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. |
| Time to Second Progression (From Start of First-Line Regimen) | Documented by Follow-up CT scans following first line treatment, average of 225 days. | Number of days from the initiation of first line treatment to first documented progression. Progression will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progression free survival (time to progression or death, whichever occurs first) is the same as time to progression as all of the patients in this trial progressed. |
Countries
United States
Participant flow
Recruitment details
Enrollment was done from 3/28/2008 to the study closure of 12/19/2011. Patients were recruited from the Oregon Health and Science University medical clinic as well as via referral from associated regional medical clinics.
Pre-assignment details
Patients were stratified according to whether they had received 5-Fluorouracil/Leucovorin with Oxaliplatin or Fluorouracil, Leucovorin, and Irinotecan for their 1st line treatment. Whichever they had not received in the 1st line setting, they received on trial. 16 patients signed consent. 2 patients withdrew, 3 ineligible, and 1 unevaluable.
Participants by arm
| Arm | Count |
|---|---|
| FOLFIRI With Erlotinib | 10 |
| FOLFOX With Erlotinib | 1 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Patient unevaluable | 1 | 0 |
Baseline characteristics
| Characteristic | FOLFIRI With Erlotinib | FOLFOX With Erlotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Categorical >=65 years | 3 participants | 0 participants | 3 participants |
| Age, Categorical Between 18 and 65 years | 6 participants | 1 participants | 7 participants |
| Region of Enrollment United States | 10 participants | 1 participants | 11 participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 1 / 1 |
| serious Total, serious adverse events | 2 / 9 | 0 / 1 |
Outcome results
Primary
Response Rates of Radiographically Measurable Disease
The primary outcome measure will be the response rates of radiographically measurable disease. Response rate of disease will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time frame: Disease response assessed after every 2 Treatment Cycles, or around 8 weeks.
Population: Patients who were considered for analysis were those who received treatment in a manner consistent with the protocol, as determined by the investigator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOLFIRI With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Complete Response | 0 Number of Patients |
| FOLFIRI With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome- Stable Disease | 5 Number of Patients |
| FOLFIRI With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Partial Response | 1 Number of Patients |
| FOLFIRI With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Progressive Disease | 4 Number of Patients |
| FOLFOX With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Progressive Disease | 0 Number of Patients |
| FOLFOX With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Complete Response | 0 Number of Patients |
| FOLFOX With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome - Partial Response | 0 Number of Patients |
| FOLFOX With Erlotinib | Response Rates of Radiographically Measurable Disease | Best Outcome- Stable Disease | 1 Number of Patients |
Secondary
Second-line Progression Free Survival
Time to disease progression from start of second-line experimental regimen. Disease progression will be measured per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time frame: Upon completion of follow-up, for an average of 99 days following the initiation of study treatment.
Population: Patients who were considered for analysis were those who received treatment in a manner consistent with the protocol, as determined by the investigator.~95% CI cannot be computed for FOLFOX with Erlotinib arm because there is only one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI With Erlotinib | Second-line Progression Free Survival | 83 Days |
| FOLFOX With Erlotinib | Second-line Progression Free Survival | 125 Days |
Secondary
Time to Second Progression (From Start of First-Line Regimen)
Number of days from the initiation of first line treatment to first documented progression. Progression will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progression free survival (time to progression or death, whichever occurs first) is the same as time to progression as all of the patients in this trial progressed.
Time frame: Documented by Follow-up CT scans following first line treatment, average of 225 days.
Population: 95% CI cannot be computed for FOLFOX with Erlotinib arm because there is only one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI With Erlotinib | Time to Second Progression (From Start of First-Line Regimen) | 83 Days |
| FOLFOX With Erlotinib | Time to Second Progression (From Start of First-Line Regimen) | 125 Days |