CALC-1 (Cetuximab in Advanced Lung Cancer): Study of 2 Methods of Combining Cetuximab and Gemcitabine in Patients With Advanced Non Small-cell Lung Cancer

The purpose of this study is to select the more promising method of combining cetuximab with gemcitabine for treating patients with advanced non small-cell lung cancer, who are not candidates for platinum based therapy.

The standard treatment for advanced non small cell lung cancer (NSCLC) is combination chemotherapy with cisplatin or carboplatin. Due to its toxicity, this therapy may not be suited for certain patients including the elderly, those whose general condition is poor. Combining chemotherapy with a biologic agent ("targeted therapy") is a new strategy being evaluated for the treatment of NSCLC, and cetuximab is one of the drugs that has shown promise for its activity and tolerability. This study aims to determine the more promising of 2 methods of combining gemcitabine with cetuximab (in combination vs. sequential administration), in two groups of patients who are not candidates for combination platinum based chemotherapy: patients under age 70 with performance status 2 (expected enrollment 42) , and patients over age 70 (expected enrollment 58).

Patients will be randomly assigned to one of two treatment arms:

* Arm A: Cetuximab + Gemcitabine:

  * Cetuximab given intravenously weekly AND
  * Gemcitabine given intravenously for a maximum of 6 cycles (on days 1 and 8 of each 3 week cycle)
* Arm B: Gemcitabine followed by Cetuximab:

  * Gemcitabine given intravenously for a maximum of 6 cycles (on days 1 and 8 of each 3 week cycle) THEN
  * Cetuximab given intravenously weekly

In Arm B, Cetuximab is administered as maintenance therapy when there has been an objective response to chemotherapy, or as second line therapy in patients who had disease progression during chemotherapy

Eligibility Criteria:
Inclusion Criteria:

* Signed written informed consent
* Age \> 18
* Histological diagnosis of non small-cell lung cancer (NSCLC)
* Stage III B or Stage IV disease
* Contraindications to platinum based therapy (age \> 70 or age \< 70 with ECOG performance status 2)
* At least one site of metastasis (target or non-target)
* Life expectancy of at least 3 months
* ECOG \<3
* Neutrophils \> 1500/mm3, platelets \> 100,000/mm3, hemoglobin \> 9g/dl
* Bilirubin \< 1.5 x the upper normal limit
* SGOT and SGPT \< 2.5 x the upper normal limits (\< 5 x the upper normal limit in the presence of hepatic metastasis)
* Creatinine \< 1.5 x the upper normal limit
* Adequate method of contraception (male and female), when there is risk of conception.

Exclusion Criteria:

* Symptomatic cerebral metastasis
* Previous chemotherapy for advanced disease
* Adjuvant chemotherapy within the previous 6 months
* Radiation therapy within previous 4 weeks
* Any experimental drug therapy within the previous 4 weeks
* Previous exposure to monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy
* Clinically relevant cardiopathy or myocardial infarct within the last 12 months
* Acute or subacute intestinal occlusion or history of inflammatory bowel disease
* Known allergy to one or more of the experimental treatments
* Known alcohol or substance abuse
* Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or give informed consent
* Pregnant or breastfeeding females
* History of malignant neoplasm within the previous 5 years (not including non-melanoma skin carcinoma and in-situ carcinoma of the uterine cervix, provided they are being adequately treated)