Clinical trial NCT00003159: Surgery With or Without Preoperative Chemotherapy in Treating Patients With Resectable Non-small Cell Lung Cancer
Official title: Randomized Trial of Surgical Resection With or Without Pre-Operative Chemotherapy in Patients With Operable Non-Small Cell Lung Cancer (NSCLC) of Any Stage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage 0 non-small cell lung cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
First posted: 2003-01-27
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if surgery is more effective with or without preoperative chemotherapy in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying surgery and preoperative chemotherapy to see how well they work compared to surgery alone in treating patients with resectable non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the survival of patients with resectable non-small cell lung cancer treated with surgery with or without preoperative chemotherapy.

Secondary

* Compare the quality of life of patients treated with these regimens.
* Compare pre-randomization clinical and post-surgical pathological staging in patients treated with these regimens.
* Compare resectability rates in patients treated with these regimens.
* Compare time to and site of relapse in patients treated with these regimens.
* Determine response in patients treated with preoperative chemotherapy.
* Determine the adverse effects of preoperative chemotherapy in these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo surgical resection no more than 4 weeks after randomization.
* Arm II: Patients receive one of the following chemotherapy regimens immediately after randomization:

  * Regimen 1: Patients receive mitomycin IV, vinblastine IV, and cisplatin IV on day 1.
  * Regimen 2: Patients receive mitomycin IV, ifosfamide IV over 3 hours, and cisplatin IV over 1 hour on day 1.
  * Regimen 3: Patients receive cisplatin IV over 2 hours on day 1 and vinorelbine IV over 5 -10 minutes on days 1 and 8.
  * Regimen 4: Patients receive paclitaxel IV and carboplatin IV on day 1.
  * Regimen 5: Patients receive gemcitabine IV on days 1 and 8 and cisplatin IV over 2 hours on day 1.
  * Regimen 6: Patients receive docetaxel IV and carboplatin IV on day 1. In all regimens, treatment repeats every 3 weeks for a total of 3 courses. Patients undergo surgical resection at least 4 weeks after the last course of chemotherapy.

Quality of life is assessed at 6 and 12 months and then annually thereafter.

Patients are followed 1 month after surgery, 6 months after randomization, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 600 patients (300 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven non-small cell lung cancer

  * Resectable disease
  * Previously untreated disease
* No evidence of distant metastases

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Neutrophil count greater than 1,500/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* Considered fit for chemotherapy and surgical resection
* No other disease or prior malignancy that would preclude study treatment
* No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent prophylactic colony-stimulating factors (except for secondary prophylaxis)
* No concurrent immunotherapy

Chemotherapy:

* Not specified

Endocrine therapy:

* No concurrent hormonal agents, except corticosteroids

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No other concurrent anticancer therapy

Primary outcomes:
measure: Survival
Secondary outcomes:
measure: Quality of life as measured by SF-36 questionnaire at baseline, 6 months, 12 months, and then annually thereafter
measure: Clinical and post-surgery pathological staging at pre-randomization
measure: Resectability rates
measure: Extent of surgery
measure: Time to and site of relapse
measure: Tumor response to chemotherapy
measure: Adverse effects of chemotherapy
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Medical Research Council Clinical Trials Unit
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
Study officials:
affiliation: Medical Research Council
name: Adrian Hodson
affiliation: Royal Marsden NHS Foundation Trust
name: Ian E. Smith, MD
References:
citation: Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, Hatton M, Hopwood P, Manegold C, Schramel F, Smit H, van Meerbeeck J, Nankivell M, Parmar M, Pugh C, Stephens R. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 2007 Jun 9;369(9577):1929-37. doi: 10.1016/S0140-6736(07)60714-4.
citation: Hopwood P, Nankivell M, Pugh C, et al.: Impact of pre-operative chemotherapy on the quality of life (QL) of patients with resectable non-small cell lung cancer (NSCLC): experience from the MRC LU22/NVALT/EORTC 08012 multicentre randomised trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-9020, 498s, 2007.
citation: Nicolson M, Gilligan D, Smith I, et al.: Pre-operative chemotherapy in patients with resectable non-small cell lung cancer (NSCLC): first results of the MRC LU22/NVALT/EORTC 08012 multi-centre randomised trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-7518, 389s, 2007.