Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Advanced Non-small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 to 75		EORTC-08975 NCT00003589

Objectives

I.  Compare the overall survival between paclitaxel/cisplatin (arm I), 
gemcitabine/cisplatin (arm II), and paclitaxel/gemcitabine (arm III) in 
patients with advanced non-small cell lung cancer.

II.  Determine the response rate, duration of response, progression-free 
survival, toxicity, and quality of life of these patients randomized in these 
three treatment arms.

Entry Criteria

Disease Characteristics:

Histologically confirmed advanced non-small cell lung cancer that is
progressive within 2 months prior to study entry
 Stage IIIB due to malignant pleural effusion or supraclavicular lymph node
  involvement only
 Stage IV
 
At least 1 bidimensionally or unidimensionally measurable target lesion 

Brain metastases or leptomeningeal disease that have been treated with
radiotherapy, is stable without medications (e.g., steroids), and asymptomatic
are allowed

Prior/Concurrent Therapy:

Biologic therapy:
 At least 4 weeks since prior immunotherapy
 No concurrent colony stimulating factor except for secondary prophylaxis in
  case of infection and severe neutropenia
 No concurrent immunotherapy

Chemotherapy:
 No prior chemotherapy for advanced disease, including intracavitary
  chemotherapy
 At least 1 year since prior neoadjuvant or adjuvant chemotherapy
 No concurrent chemotherapy

Endocrine therapy:
 See Disease Characteristics
 No concurrent hormonal agents (except corticosteroids for antiemetic
  prophylaxis)

Radiotherapy:
 Prior radiotherapy should not include all target lesions for evaluation
 At least 4 weeks since prior radiotherapy
 Concurrent palliative radiotherapy allowed if indicator lesion is outside of
  radiation field 

Surgery:
 Not specified

Patient Characteristics:

Age:
 18 to 75

Performance status:
 WHO 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Absolute neutrophil count at least 2,000/mm3
 Platelet count at least 100,000/mm3
 Prothrombin time less than 1.5 times normal

Hepatic:
 Bilirubin no greater than 1.25 times upper limit of normal (ULN) (no greater
  than 2.5 times ULN if due to liver metastases)
 AST or ALT less than 3 times ULN (no greater than 5 times ULN if due to liver
  metastases)

Renal:
 Creatinine clearance at least 60 mL/min

Cardiovascular:
 No uncontrolled cardiac disease, sign of cardiac failure, or rhythm
  disturbances requiring medication
 No myocardial infarction in the past 3 months

Neurological:
 No preexisting motor or sensory neurotoxicity of grade 2 or greater

Other:
 No active uncontrolled infection
 Not a poor medical risk due to nonmalignant disease
 No secondary primary malignancy in the past 5 years (excluding melanoma,
  breast cancer, and hypernephroma) except carcinoma in situ of the cervix or
  adequately treated basal cell carcinoma of the skin  
 No psychological condition that might hamper compliance in this study
 Not pregnant
 Effective contraception required of all fertile patients during and for 3
  months after study

Expected Enrollment

A total of 450 patients (150 patients per arm) will be accrued into this study 
over 36 months.

Outline

This is randomized, multicenter study.  Patients are stratified according to 
performance status (0-1 vs 2) and stage of disease (locally advanced vs 
metastatic).

Patients are randomized to receive paclitaxel IV over 3 hours on day 1 
followed by cisplatin IV on day 1 every 3 weeks (arm I), gemcitabine IV over 
30-60 minutes on days 1 and 8 and cisplatin IV on day 1 every 3 weeks (arm 
II), or paclitaxel IV over 3 hours on day 1 followed by gemcitabine IV over 
30-60 minutes on days 1 and 8 every 3 weeks (arm III).  Patients receive at 
least 2 courses of treatment.  In the absence of unacceptable toxicity and 
disease progression, patients may receive up to 6 courses of treatment.

Quality of life is assessed before, during, and at the end of treatment, then 
every 6 weeks until disease progression, and then every 3 months until death.

Patients are followed every 6 weeks until disease progression, then every 3 
months until death.

Efficace F, Bottomley A, Smit EF, et al.: Is a patient's self-reported health-related quality of life a prognostic factor for survival in non-small-cell lung cancer patients? A multivariate analysis of prognostic factors of EORTC study 08975. Ann Oncol 17 (11): 1698-704, 2006.[PUBMED Abstract]

Smit EF, van Meerbeeck JP, Lianes P, et al.: Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol 21 (21): 3909-17, 2003.[PUBMED Abstract]

Giaccone G: Gemcitabine plus taxane combinations in non-small cell lung cancer. Semin Oncol 26 (1 Suppl 4): 19-24, 1999.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Egbert Smit, MD, Protocol chair		Ph: 31-20-444-4752

Registry Information
Official Title		Randomized Study with New Combination Chemotherapies in Advanced Non-Small Cell Lung Cancer
Trial Start Date		1998-08-17
Registered in ClinicalTrials.gov		NCT00003589
Date Submitted to PDQ		1998-09-24
Information Last Verified		2007-05-21