This trial is designed to investigate the safety, tolerability and the effectiveness when OSI-774 (tarceva) is combined with oxaliplatin and capecitabine in treating patients with metastatic colorectal cancer.

Condition	Intervention	Phase
Colorectal Cancer Neoplasm Metastasis	Drug: Tarceva (OSI-774)  Drug: Capecitabine  Drug: Oxaliplatin	Phase II

Further Study Details: 

Primary Outcomes: To determine the response rate of OSI-774 when given in combination with oxaliplatin and capecitabine in patients with previously-treated locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma
Secondary Outcomes: To assess overall survival, progression-free survival, time to progression and duration of response; To evaluate the toxicities of the combination of OSI-774, oxaliplatin and capecitabine in this population of patients with colorectal cancer
Expected Total Enrollment:  32

Patients will be treated with OSI-774 (orally) daily, oxaliplatin (intravenously) every 3 weeks, and capecitabine (orally) twice daily for 14 days followed by a 7-day rest period. This will constitute a 21-day treatment cycle. Treatment will continue until disease progression or unacceptable toxicity occurs.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document.
• Patients with histologic proof of adenocarcinoma of the colon or rectum (colorectal carcinoma) with evidence of metastatic disease.
• Patients must have received one (and only 1) prior chemotherapy regimen for metastatic disease. Patients who received adjuvant therapy and then 1 regimen for metastatic disease are eligible. Patients who received adjuvant therapy and recur within 12 months of completion of adjuvant therapy are also eligible.
• Patients who have received prior radiation therapy, either in the adjuvant or metastatic setting, for colorectal carcinoma.

• All of the following must apply:

  • Greater than 4 weeks must have elapsed from the time of major surgery and patients must have recovered from the effects (e.g., laparotomy); *Greater than 2 weeks must have elapsed from the time of minor surgery and patients must have recovered from the operation. (Insertion of a vascular access device is not considered major or minor surgery.);
  • Greater than 4 weeks must have elapsed from the time of major radiotherapy [RT] (e.g., chest or bone palliative RT);
  • Greater than 4 weeks must have elapsed from the completion of previous chemotherapy and patients must have recovered from any related toxicities;
  • Greater than 4 weeks must have elapsed from the participation in any investigational drug study.
• ECOG performance status < 2 ; life expectancy > 12 weeks
• Patients must have normal organ and marrow function as defined below:

ANC > 1500/mm3; hemoglobin > 9.0 gm/dl; platelets > 100,000/mm3; SGOT < 2.5x upper limits of normal if no evidence of liver metastases or < 5x upper limits of normal if evidence of liver metastases; total bilirubin < 1.5x upper limits of normal; Alk Phos < 2.5x upper limits of normal (or < 5x upper limits of normal if evidence of liver metastases or < 10x upper limits of normal if evidence of bone disease).

Exclusion Criteria:

• Patients with peripheral neuropathy of grade 2 or greater severity.
• Uncontrolled high blood pressure.
• Unstable angina.
• Symptomatic congestive heart failure.
• Myocardial infarction < 12 months prior to registration.
• Serious uncontrolled cardiac arrhythmia.
• New York Heart Association classification III or IV.
• Active or uncontrolled infection.
• Medical or psychiatric conditions which, in the opinion of the investigator, make participation in an investigational trial of this nature a poor risk.
• Patients with known brain metastases or carcinomatous meningitis should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• No concurrent malignancy of any site, except for limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration and agree to use an effective method of contraception.
• Patients who are pregnant or lactating.
• Patients with prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil.
• Patients previously treated with oxaliplatin, OSI-774 or another epidermal growth factor inhibitor (EGFR).
• Patients lacking physical integrity of the upper gastrointestinal tract.
• Patients with other serious uncontrolled medical conditions that the investigator feels might compromise study participation.

Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02115,  United States

Study chairs or principal investigators

Jeffrey A. Meyerhardt, MD,  Principal Investigator,  Dana-Farber Cancer Institute   

Study ID Numbers:  02-269
Last Updated:  August 3, 2005
Record first received:  July 25, 2005
ClinicalTrials.gov Identifier:  NCT00123851
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-23