Ph II Gemcitabine, Erlotinib, and Gemcitabine With Erlotinib/Elderly Patients W/ IIIB/IV NSCLC

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether gemcitabine and erlotinib are more effective when given alone or together in treating non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying gemcitabine and erlotinib to compare how well they work when given alone or together as first-line therapy in treating older patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the progression-free survival rate of older patients with stage IIIB or IV non-small cell lung cancer treated with gemcitabine hydrochloride vs erlotinib hydrochloride vs gemcitabine hydrochloride and erlotinib hydrochloride as first-line therapy. Secondary Determine the response rate in patients receiving these regimens. Determine the overall survival rate in patients receiving these regimens. Determine the toxicity profile of these regimens in these patients. Determine the quality of life of patients receiving these regimens. OUTLINE: This is a randomized, open-label, controlled, parallel group, multicenter study. Patients are stratified by gender, smoking status (never or light vs current or former), and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV on days 1 and 8. Patients with progressive disease may cross over to arm II. Arm II: Patients receive oral erlotinib hydrochloride daily on days 1-21. Arm III: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride as in arm II. In all arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 2 months for 3 years.

Official Title
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Randomized Phase II Study of First-Line Treatment With Gemcitabine vs. Erlotinib vs. Gemcitabine and Erlotinib in Elderly Patients With Stage IIIB/IV Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologic or cytologic diagnosis of stage NSCLC ECOG Performance Status (PS) 0-2 Absolute Neutrophil Count (ANC) ≥ 1.5 Platelets ≥ 100,000 Hemoglobin ≥ 8.0 g/dl Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 upper limit of institutional normal (ULN) Alkaline phosphatase ≤ 4 x ULN Total Bilirubin below or equal to upper institutional normal limits Serum Creatinine ≤ 1.5 x ULN Patients may have received 1 prior treatment in the adjuvant setting, but time since prior chemotherapy must be ≥1 year. Although the protocol specifically says adjuvant therapy, we believe neoadjuvant is similar and patients who have received neo-adjuvant (pre-operative) rather than classic adjuvant (post-operative) therapy are similar and should not be distinguished. Therefore, patients may have received 1 prior treatment in the neo-adjuvant setting as well. Treated brain metastases are eligible provided the patient is asymptomatic and meets the above criteria, including PS. Measurable disease by RECIST criteria Ability to give informed consent Exclusion Criteria Patients with a history of severe hypersensitivity to gemcitabine. Incompletely healed from previous oncologic or other major surgery. Pregnancy or breast feeding (women of childbearing potential are not expected to be enrolled in this study given minimum age) Patients with severe co-morbid illness. Patients unable to participate in the QOL assessments.

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 120 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B. | Drug: gemcitabine hydrochloride<br>* given IV<br>* Other names: Gemzar;|
| Experimental: Arm B<br>Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21. | Drug: erlotinib hydrochloride<br>* given orally<br>* Other names: Tarceva;|
| Experimental: Arm C<br>Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily | Drug: erlotinib hydrochloride<br>* given orally<br>* Other names: Tarceva;Drug: gemcitabine hydrochloride<br>* given IV<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | We would consider the combination of gemcitabine plus erlotinib or single agent erlotinib to be worthy of further study if there was an increased progressed-free survival. We would use an increase to 45% progression-free survival at 6 months as significant. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | The best overall response (BOR) is the best response recorded from the start of the treatment until disease progression-recurrence (taking as reference for progressive disease the smallest measurement recorded since the treatment started. The response rate was defined as the percentage of patients achieving a BOR of complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Six months | 
| Overall Survival | Survival calculated from start of treatment to death from any cause for up to three years. | Up to 3 years | 
| Toxicity | Assessments for treatment toxicity will be done with each cycle according to CTCAE v3. Results listed here are grade >=3, treatment related hematologic events (all) and Grade>=3 treatment related non hematologic events that occurred in >=5% of patients in any arm. Adverse events (toxicities) are graded on a 5 point scale from 1 (mild) to 5 (lethal), with grades 3 and higher being severe or life threatening. | After each cycle/3 weeks, up to 3 years | 
| Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) | The FACT-L is the FACT-G and a lung cancer specific (LCS) subscale given at baseline, after each cycle and at end of treatment. The FACT-G is a 27 item measure of general QOL assessing function in 4 domains: physical well-being (PWB), social-family well-being (SFWB), emotional well-being (EWB) and functional well-being (FWB). Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL. The TOI-L sums the PWB, FWB, and LCS subscale scores. A best response for TOI-L scores is based on change from baseline and coded as: a change >=+6 improved, <= -6 worsened and otherwise no change. A best overall score response is coded as: Improved (2 visit resp. of improved a min. of 28 days apart w/ no interim worsened) No change (not improved; 2 visit resp. of no change or improved a min. of 28 days apart w/ no interim worsened) Worsened (not improved or no change; 2 consecutive worsened) Other (none of the above) | After each cycle/3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer