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

UNC Lineberger Comprehensive Cancer Center147 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 70 YearsMax age: 120 Years

Medical Language ↔ Plain English

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.

Locations (11)

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas, United States

Summit Cancer Care

Savannah, Georgia, United States

Evanston Hospital

Evanston, Illinois, United States

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Batte Cancer Center at Northeast Medical Center

Concord, North Carolina, United States

Cape Fear Valley Medical Center Cancer Center

Fayetteville, North Carolina, United States

Rex Cancer Center at Rex Hospital

Raleigh, North Carolina, United States

Kingsport Hematology-Oncology Associates

Kingsport, Tennessee, United States

...and 1 more locations

Outcomes

Primary Outcomes

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.

Time frame: Six months

Secondary Outcomes

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.

Time frame: Six months

Overall Survival

Survival calculated from start of treatment to death from any cause for up to three years.

Time frame: 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.

Time frame: 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)

Time frame: After each cycle/3 weeks