Pemetrexed Disodium Plus Gemcitabine in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Phase II Clinical Trial Evaluating Three Schedules Of ALIMTA Plus Gemcitabine As Frontline Chemotherapy For Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug and giving the drugs in different ways may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of three different regimens of pemetrexed disodium plus gemcitabine in treating patients who have locally advanced or metastatic non-small cell lung cancer.

Study Overview

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

Detailed Description

OBJECTIVES:

• Compare the tumor response rates in patients with locally advanced or metastatic non-small cell lung cancer treated with 3 different schedules of pemetrexed disodium and gemcitabine.
• Compare the duration of response, time to progressive disease, time to treatment failure, and survival time in patients treated with these regimens.
• Compare the quantitative and qualitative toxic effects of these regimens in these patients.

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

• Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1 followed by gemcitabine IV over 30 minutes on days 1 and 8.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by pemetrexed disodium IV over 10 minutes on day 1.
• Arm III: Patients receive gemcitabine IV over 30 minutes on day 1 and pemetrexed disodium IV over 10 minutes followed by gemcitabine IV over 30 minutes on day 8.

Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive up to 6 additional courses of therapy.

Patients are followed every 2 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 180 patients (60 per treatment arm) will be accrued for this study within 20 months.

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Health Plaza
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Health System
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
    • Grand Forks, North Dakota, United States, 58201
      • Altru Health Systems
  • Ohio
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • CCOP - Geisinger Clinic and Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer

  • Stage IIIB disease that is ineligible for combined modality therapy OR
  • Stage IV disease
• Measurable disease
• No clinically detectable (by physical exam) third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures
• No brain metastases (even if treated)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 3 times ULN (5 times ULN if liver metastases present)

Renal:

• Creatinine clearance at least 45 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take folic acid or cyanocobalamin (vitamin B12) supplementation
• No uncontrolled infection
• No concurrent chronic debilitating disease
• No weight loss of 10% or more within the past 6 weeks
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic or genetic therapy for lung cancer
• No concurrent immunomodulating agents

Chemotherapy:

• No prior chemotherapy for lung cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy to a different site and recovered
• No prior radiotherapy to 25% or more of bone marrow
• No prior radiotherapy to whole pelvis
• No prior radiotherapy for primary disease
• No concurrent radiotherapy

Surgery:

• More than 4 weeks since prior major surgery

Other:

• No aspirin or nonsteroidal anti-inflammatory agents 2 days before, during, and for 2 days after pemetrexed disodium administration (5 days for long-acting agents such as piroxicam, naproxen, diflunisal, or nabumetone)
• No other concurrent cytostatic or cytotoxic therapy

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I: pemetrexed + gemcitabine; Patients receive pemetrexed disodium IV over 10 minutes on day 1 followed by gemcitabine IV over 30 minutes on days 1 and 8.	Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium
Experimental: Arm II: pemetrexed + gemcitabine; Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by pemetrexed disodium IV over 10 minutes on day 1.	Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium
Experimental: Arm III: pemetrexed + gemcitabine; Patients receive gemcitabine IV over 30 minutes on day 1 and pemetrexed disodium IV over 10 minutes followed by gemcitabine IV over 30 minutes on day 8.	Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor response rate	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
duration of response	Up to 4 years
time to treatment failure	Up to 4 years
survival	Up to 4 years
time to disease progression	Up to 4 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Jatoi A, Hillman S, Stella P, Green E, Adjei A, Nair S, Perez E, Amin B, Schild SE, Castillo R, Jett JR; North Central Cancer Treatment Group. Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol. 2005 Dec 20;23(36):9113-9. doi: 10.1200/JCO.2005.03.7465.
• An MW, Mandrekar SJ, Branda ME, Hillman SL, Adjei AA, Pitot HC, Goldberg RM, Sargent DJ. Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials. Clin Cancer Res. 2011 Oct 15;17(20):6592-9. doi: 10.1158/1078-0432.CCR-11-0822. Epub 2011 Aug 31.
• Campbell ME, Mandrekar SJ, Hillman SL, et al.: What is the added value of actual tumor measurements (TM) in predicting overall survival (OS)? The North Central Cancer Treatment Group (NCCTG) findings. [Abstract] J Clin Oncol 26 (Suppl 15): A-6520, 2008.
• Adjei AA, Salavaggione OE, Mandrekar SJ, Dy GK, Ziegler KL, Endo C, Molina JR, Schild SE, Adjei AA. Correlation between polymorphisms of the reduced folate carrier gene (SLC19A1) and survival after pemetrexed-based therapy in non-small cell lung cancer: a North Central Cancer Treatment Group-based exploratory study. J Thorac Oncol. 2010 Sep;5(9):1346-53. doi: 10.1097/JTO.0b013e3181ec18c4.
• Ma CX, Nair S, Thomas S, Mandrekar SJ, Nikcevich DA, Rowland KM, Fitch TR, Windschitl HE, Hillman SL, Schild SE, Jett JR, Obasaju C, Adjei AA; North Central Cancer Treatment Group; Mayo Clinic; Eli Lilly & Company. Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5929-37. doi: 10.1200/JCO.2005.13.953.

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

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; 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: NCCTG-N0026; NCI-2012-02399 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000068838 (Registry Identifier: PDQ (Physician Data Query))