Erlotinib and Chemotherapy for 2nd Line Treatment (Tx) of Metastatic Colorectal Cancer (mCRC)

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Study of Erlotinib (Tarceva) Alternating With Chemotherapy for Second-line Treatment of Metastatic Colorectal Cancer With Molecular Correlates for p53 Pathway

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFOX with Erlotinib<br>Subjects received FOLFOX (Leucovorin, Fluorouracil, and Oxaliplatin) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFOX on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22. | Drug: Erlotinib<br>* 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.<br>* Other names: Tarceva;Drug: Fluorouracil<br>* 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.<br>Drug: Leucovorin<br>* Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.<br>Drug: Oxaliplatin<br>* Platinum-based antineoplastic chemotherapy agent given intravenously at 85 mg/m2.<br>|
| Experimental: FOLFIRI with Erlotinib<br>Subjects received FOLFIRI (Leucovorin, Fluorouracil, and Irinotecan) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFIRI on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22. | Drug: Erlotinib<br>* 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.<br>* Other names: Tarceva;Drug: Fluorouracil<br>* 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.<br>Drug: Leucovorin<br>* Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.<br>Drug: Irinotecan<br>* Chemotherapy agent given intravenously at 180 mg/m2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Disease response assessed after every 2 Treatment Cycles, or around 8 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Upon completion of follow-up, for an average of 99 days following the initiation of study treatment. | 
| 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. | Documented by Follow-up CT scans following first line treatment, average of 225 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colon, Cancer, Metastatic, Colorectal