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

Phase 2

Terminated

Conditions: Metastatic Colorectal Cancer

Interventions: Drug: Erlotinib
Drug: Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Irinotecan

Registration Number: NCT00642746

Lead Sponsor: OHSU Knight Cancer Institute

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFOX with Erlotinib	Fluorouracil	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.
FOLFOX with Erlotinib	Erlotinib	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.
FOLFOX with Erlotinib	Leucovorin	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.
FOLFOX with Erlotinib	Oxaliplatin	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.
FOLFIRI with Erlotinib	Erlotinib	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.
FOLFIRI with Erlotinib	Fluorouracil	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.
FOLFIRI with Erlotinib	Irinotecan	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.
FOLFIRI with Erlotinib	Leucovorin	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.