Ph II Gemcitabine, Erlotinib, and Gemcitabine With Erlotinib/Elderly Patients W/ IIIB/IV NSCLC
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.
|Lung Cancer||Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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|
- Progression-free Survival [ Time Frame: Six months ]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.
- Response Rate [ Time Frame: Six months ]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.
- Overall Survival [ Time Frame: Up to 3 years ]Survival calculated from start of treatment to death from any cause for up to three years.
- Toxicity [ Time Frame: After each cycle/3 weeks, up to 3 years ]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.
- Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) [ Time Frame: After each cycle/3 weeks ]
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)
|Study Start Date:||March 2006|
|Study Completion Date:||October 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Arm A
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
Other Name: Gemzar
Experimental: Arm B
Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.
Drug: erlotinib hydrochloride
Other Name: Tarceva
Experimental: Arm C
Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Drug: erlotinib hydrochloride
Other Name: TarcevaDrug: gemcitabine hydrochloride
Other Name: Gemzar
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00283244
|United States, Arkansas|
|Highlands Oncology Group - Fayetteville|
|Fayetteville, Arkansas, United States, 72703|
|United States, Georgia|
|Summit Cancer Care|
|Savannah, Georgia, United States, 31405|
|United States, Illinois|
|Evanston, Illinois, United States, 60201-1781|
|United States, New Jersey|
|Hackensack University Medical Center Cancer Center|
|Hackensack, New Jersey, United States, 07601|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Blumenthal Cancer Center at Carolinas Medical Center|
|Charlotte, North Carolina, United States, 28232-2861|
|Batte Cancer Center at Northeast Medical Center|
|Concord, North Carolina, United States, 28025|
|Cape Fear Valley Medical Center Cancer Center|
|Fayetteville, North Carolina, United States, 28302-2000|
|Rex Cancer Center at Rex Hospital|
|Raleigh, North Carolina, United States, 27607|
|United States, Tennessee|
|Kingsport Hematology-Oncology Associates|
|Kingsport, Tennessee, United States, 37660|
|University of Tennessee Cancer Institute - Memphis|
|Memphis, Tennessee, United States, 38104|
|Principal Investigator:||Thomas E Stinchcombe, MD||UNC Lineberger Comprehensive Cancer Center|