Pemetrexed Disodium and Gemcitabine in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

A Randomized Phase II Study of ALIMTA® (Pemetrexed) and GEMZAR® (Gemcitabine) Every 14 Days Versus Pemetrexed and Gemcitabine Every 21 Days in Advanced Non-Small Cell Lung Cancer

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving pemetrexed disodium together with gemcitabine may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different schedules of pemetrexed disodium and gemcitabine to compare how well they work in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gemcitabine HCL; Drug: pemetrexed disodium; Drug: gemcitabine HCL

Detailed Description

OBJECTIVES:

Primary

• Compare response rates in patients with stage IIIB or IV non-small cell lung cancer treated with two different treatment schedules of pemetrexed disodium and gemcitabine hydrochloride.

Secondary

• Compare time-to-event efficacy variables in patients treated with these regimens.
• Compare progression-free and overall survival of patients treated with these regimens.
• Determine the overall toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to disease stage (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • Stage IIIB (with controlled pleural effusion) OR stage IV disease
• At least 1 measurable lesion whose longest diameter is ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No medically significant third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures

• No documented brain metastases unless all of the following criteria are met:

  • Successful local therapy has been completed
  • At least 2 weeks since prior corticosteroids
  • Brain imaging required for symptomatic patients only (to rule out brain metastases)
• Concurrent enrollment in clinical trial MCCRC-RC0527 required

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks
• ECOG performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• AST and ALT ≤ 3 times ULN (5 times ULN for liver involvement)
• Creatinine clearance ≥ 45 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take folic acid, cyanocobalamin (vitamin B12) supplementation, or dexamethasone and corticosteroids
• Able to interrupt intake of aspirin and nonsteroidal anti-inflammatory agents for a total of 5 days

• No severe and/or uncontrolled medical conditions, including any of the following:

  • Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
  • Angina pectoris
  • Congestive heart failure within the past 3 months, unless ejection fraction > 40%
  • Myocardial infarction within the past 6 months
  • Cardiac arrhythmia
  • Diabetes
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • New York Heart Association class III or IV heart disease
  • Clinically significant infection
• No other serious medical condition or illness that would preclude study participation
• No peripheral neuropathy ≥ grade 2
• No other malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate cancer
• No significant weight loss (≥ 10%) within the past 6 weeks
• No investigator site personnel directly affiliated with the study, or immediate family (i.e., spouse, parent, child, or sibling, whether biological or legally adopted)

• No employees of Eli Lilly (i.e., employees, temporary contract workers, or designees responsible for conducting the study)

  • Immediate family of Eli Lilly employees may participate in Eli Lilly-sponsored clinical trials, but are not permitted to participate at an Eli Lilly facility

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 weeks since prior corticosteroids
• At least 4 weeks since prior radiation therapy involving > 25% of the bone marrow and recovered
• At least 30 days since prior investigational therapy
• No prior radiation therapy to the whole pelvis
• No prior systemic chemotherapy for advanced non-small cell lung cancer
• No prior pemetrexed disodium and/or gemcitabine hydrochloride
• No prior or concurrent sorafenib tosylate and/or temsirolimus
• No concurrent Hypericum perforatum (St. John's wort)
• No other concurrent antitumor therapy
• No concurrent agents that stimulate thrombopoiesis
• Concurrent palliative radiation therapy allowed
• Concurrent corticosteroids allowed for adrenal insufficiency or severe nausea and vomiting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemzar x2; Treat subjects with 2 dosings/cycle of Gemzar x6 cycles.	Drug: gemcitabine HCL; 1250 mg/m^2 administered through 250 cc NS (normal saline) IV (intravenous) infusion over 30 minutes at days 1 & 8 of each cycle (21 days) x6 cycles.; Other Names: GEMZAR; Drug: pemetrexed disodium; 500 mg/m^2 administered through 100 mL NS IV infusion over 10 minutes at day 1 of each cycle.; Other Names: ALIMTA; Drug: gemcitabine HCL; 1500 mg/m^2 administered through 250 cc NS IV infusion over 30 minutes at days 1 of each cycle (14 days) x9 cycles.; Other Names: GEMZAR
Experimental: Gemzar x1; Treat subjects with 1 dosing/cycle of Gemzar x9 cycles.	Drug: gemcitabine HCL; 1250 mg/m^2 administered through 250 cc NS (normal saline) IV (intravenous) infusion over 30 minutes at days 1 & 8 of each cycle (21 days) x6 cycles.; Other Names: GEMZAR; Drug: pemetrexed disodium; 500 mg/m^2 administered through 100 mL NS IV infusion over 10 minutes at day 1 of each cycle.; Other Names: ALIMTA; Drug: gemcitabine HCL; 1500 mg/m^2 administered through 250 cc NS IV infusion over 30 minutes at days 1 of each cycle (14 days) x9 cycles.; Other Names: GEMZAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Confirmed Responses	Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. > > Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions.	Two consecutive evaluations at least 6 weeks apart (up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation.	Time from registration to progression or death (up to 2 years)
Overall Survival	Overall survival time was defined as the number of months from registration to the date of death or last follow-up	Death or last follow-up (up to 2 years)
Adverse Event	Number of patients that experienced adverse events (grade 4 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0	Gemzar x2 Arm every 21 days, Gemzar x1 Arm every 14 days (up to 2 years)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Julian Molina, MD, PhD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2006
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): May 12, 2010

Study Registration Dates

• First Submitted: December 4, 2006
• First Submitted That Met QC Criteria: December 4, 2006
• First Posted (Estimate): December 5, 2006

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; 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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Folic Acid Antagonists; Gemcitabine; Pemetrexed
• Other Study ID Numbers: CDR0000516012; P30CA015083 (U.S. NIH Grant/Contract); 06-002282 (Other Identifier: Mayo Clinic IRB); RC0524 (Other Identifier: Mayo Clinic Cancer Center & MCCRC); H3E-US-S061 (Lilly Protocol)