Erlotinib in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer (TOPICAL)

• Progression free survival [ Time Frame: from the date of randomisation to the date of first clinical evidence of progressive disease, or death. ] [ Designated as safety issue: No ]
• Adverse events/Toxicity [ Time Frame: during and for 28 days following Tarceva/placebo treatment ] [ Designated as safety issue: Yes ]
• Quality of life [ Time Frame: between randomisation and 8 weeks. ] [ Designated as safety issue: No ]
  QL will be measured using the patient-completed EORTC-QLQ C30 and lung cancer module (LC 14). The primary QL outcome measures will be changes in overall QL and the five most commonly reported lung cancer symptoms (fatigue, breathlessness, cough, emotional functioning and pain).
• Cost-effectiveness [ Time Frame: from date of randomisation to death ] [ Designated as safety issue: No ]
  Effectiveness will be estimated in terms of quality-adjusted life years. Mean survival will be calculated on the basis of observed mortality (i.e. a within-trial estimate) and by extrapolating the survival curves if some patients remain alive at the end of the trial.

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether erlotinib is more effective than a placebo in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying erlotinib to see how well it works compared to a placebo in treating patients with stage III or stage IV non-small cell lung cancer.

OBJECTIVES:

Primary

• Compare survival of patients with stage IIIB or IV non-small cell lung cancer that is not suitable for first-line chemotherapy treated with erlotinib vs placebo.

Secondary

• Compare progression-free survival and response rate.
• Compare toxicity.
• Compare the quality of life.
• Compare cost-effectiveness.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral erlotinib once daily for up to 24 months.
• Arm II: Patients receive oral placebo once daily for up to 24 months. Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 664 patients will be accrued for this study.

• Drug: erlotinib hydrochloride
  Tarceva (OSI-774, erlotinib) PO 150 mg daily
  Other Names:

  • OSI-774
  • Tarceva
• Drug: Matched placebo
  Matched placebo PO daily

• Experimental: Erlotinib
  Tarceva (OSI-774, erlotinib) PO 150mg daily
  Intervention: Drug: erlotinib hydrochloride
• Placebo Comparator: Matched placebo
  Matched placebo PO daily
  Intervention: Drug: Matched placebo

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Advanced disease (stage IIIB or IV)
  • Diagnosis within 62 days prior to randomization

• Not suitable for first-line chemotherapy, as defined by the following criteria*:

  • ECOG performance status 2-3
  • ECOG performance status 0-1 AND creatinine clearance < 60 mL/min
• NOTE: *These criteria do not imply that all such patients are unsuitable for chemotherapy; patients are considered unsuitable on a case by case basis
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

• Estimated life expectancy of at least 8 weeks
• Able to take oral medication
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No severe uncontrolled infection
• No unstable angina
• No myocardial infarction within the past month
• No uncontrolled inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
• No acute renal failure
• Bilirubin < 2 times upper limit of normal (ULN)
• Transaminases < 2 times ULN (5 times ULN if liver metastases are present)
• Creatinine < 5 times ULN
• No evidence of other significant laboratory finding or uncontrolled medical illness that would interfere with study treatment or results comparison or render the patient at high risk from treatment complications
• No other prior or current malignant disease likely to interfere with study treatment or comparisons

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No prior biological anticancer therapy (e.g., gefitinib, thalidomide, or cetuximab)

• No prior palliative radiotherapy

  • Prior palliative radiotherapy to bone metastases allowed within the past 2 weeks
• No concurrent cyclooxygenase-2 inhibitors

• Cancer Research UK
• Roche Pharma AG