Erlotinib and Docetaxel in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Failure of One Chemotherapy Regimen

Study Overview
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Brief Summary
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Erlotinib has demonstrated efficacy as a single agent in patients with NSCLC and the addition of erlotinib to chemotherapy has not achieved better results in the general population. However, several preclinical and phase I studies have shown that a sequential treatment of erlotinib and chemotherapy could avoid a possible negative interaction between both drugs when administrated concomitantly, and therefore, it could improve the benefit of the combination therapy. This study will investigate if the intermittent treatment of a chemotherapy drug, such as docetaxel, with erlotinib could achieve a clinical benefit.

Official Title
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Phase II, Multicenter, Randomized, Open Label Study of a Sequential Treatment of Intermittent Erlotinib and Docetaxel Versus Erlotinib in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer After Failure of a Prior Chemotherapy Regimen

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Docetaxel and Erlotinib
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Age >= 18 years. Histologically or cytologically documented inoperable, locally advanced (stage IIIb with malignant pleural or pericardial effusion) or metastatic (Stage IV) NSCLC. Patients who have failed only one prior chemotherapy to treat the advanced disease and candidates to receive a second line treatment. ECOG PS 0-2. Adequate hematological function: hemoglobin => 9 g/dl; neutrophils count => 1.5 x 10(9)/l; platelet count => 100 x 10(9)/l. Adequate liver function: Bilirubin <= 1,5 x ULN; AST and ALT <= x 3 ULN when no hepatic metastases or <=5 x ULN if hepatic metastases; Alkaline phosphatase <=5 x UNL except that there is hepatic metastases. Adequate renal function: Calculated creatinine clearance => 40 mL/min (Cockroft y Gault) or serum creatinine <= 1.5 x ULN . Patient able to meet the requirements of the study and accessible for correct follow-up. Oral swallowing capability. Exclusion Criteria: Previous treated with more than one chemotherapeutic treatment for NSCLC Concomitant treatment with another drug under investigation. Pregnancy or lactation. Fertile women must provide a negative result of pregnancy test (in serum or urine) within 7 days prior to study treatment start. In addition, they must use an effective method of contraception (oral contraceptives, intrauterine device, barrier methods of contraception, together with spermicidal jelly or surgical sterilization) during the study. Evidence of other disease, metabolic or neurological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications. Contraindication for the use of erlotinib or docetaxel.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel and Erlotinib<br>Patients in the experimental arm will receive sequential treatment of intermittent erlotinib and docetaxel up to 4 cycles in the absence of disease progression, unacceptable toxicity, patient refusal or investigator's decision to discontinue the treatment. After 4 cycles, participants will receive 150 mg of erlotinib per day until disease progression, unacceptable toxicity, patient refusal or investigator's decision to discontinue the treatment. | Drug: Docetaxel and Erlotinib<br>* Docetaxel (Taxotere®) 75 mg/m2 iv first day of each 21-day cycle. Erlotinib (Tarceva®) 150 mg po days 2-16 of each 21-day cycle. Total: 4 cycles in the absence of disease progression<br>|
| Active Comparator: Erlotinib<br>Erlotinib (Tarceva®) 150 mg/day po daily until disease progression, unacceptable toxicity, patient refusal or investigator's decision to discontinue the treatment. | Drug: Erlotinib<br>* 150 mg/day po daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients without disease progression after 6 months of treatment. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Time from randomization until objective tumor progression or death for any cause. Tumour progression will be assessed every 2 months. | 
| Duration of Response |  | The time from the first complete response or partial response until objective tumor progression or death due to progression disease. Tumour progression will be assessed every 2 months. | 
| Overall Response Rate |  | The proportion of patients with tumor size reduction (complete response or partial response following RECIST criteria). Response will be assessed every 2 months. | 
| Disease Control Rate |  | The proportion of patients without tumor size increase (complete response, partial response or stable disease following RECIST criteria). Response wil be assessed every 2 months. | 
| Overall survival |  | Time from randomization until death from any cause. Follow up wil be assessed every 3 months after finishing study treatment. | 
| Safety profile |  | Toxicity will be discribed per cycle and per patient according to CTCAE vs. 3, every 3 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma, Carcinoma, Non-Small Cell, Lung Neoplasms, Docetaxel, Erlotinib, Chemotherapy