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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: gemcitabine hydrochloride

Detailed Description

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
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group - Fayetteville
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Summit Cancer Care
  • Illinois
    • Evanston, Illinois, United States, 60201-1781
      • Evanston Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Concord, North Carolina, United States, 28025
      • Batte Cancer Center at Northeast Medical Center
    • Fayetteville, North Carolina, United States, 28302-2000
      • Cape Fear Valley Medical Center Cancer Center
    • Raleigh, North Carolina, United States, 27607
      • Rex Cancer Center at Rex Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Kingsport Hematology-Oncology Associates
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute - Memphis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 120 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; given IV; Other Names: Gemzar
EXPERIMENTAL: Arm B; Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.	Drug: erlotinib hydrochloride; given orally; Other Names: 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; given orally; Other Names: Tarceva; Drug: gemcitabine hydrochloride; given IV; Other Names: Gemzar

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Thomas E Stinchcombe, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (ESTIMATE): January 27, 2006

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Erlotinib Hydrochloride
• Other Study ID Numbers: LCCC 0512; P30CA016086 (U.S. NIH Grant/Contract); UNC-LCCC-0512 (OTHER: UNC IRB #05-2256)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share any individual participant data.