GILT Docetaxel - Non-Small Cell Lung Cancer

Open-Label, Cooperative, Randomized, Multicenter Phase III Study on the Use of Cisplatin Resistant Genotype (ERCC1 Over-Expression) in Tumor RNA to Customize Chemotherapy in Stage IV-IIIB (Malignant Pleural Effusion) Non-Small-Cell Lung Cancer Patients

Primary Objective:

• To compare response rate between genotypic groups and control group.

Secondary Objective:

• To determine the safety, time to treatment failure and survival in control and genotypic arms.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasms
• Intervention / Treatment: Drug: docetaxel/gemcitabine; Drug: Docetaxel/DDP

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Sanofi-Aventis
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis
• Switzerland
  • Genève, Switzerland
    • Sanofi-Aventis

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

Inclusion Criteria:

Patients must be/have:

• histologically confirmed non-small cell lung cancer (squamous cell carcinoma, large cells or adenocarcinoma; it is recommended to provide the full paraffin-embedded block or at least 5 5 sections obtained from the primary tumor, recurrence or metastasis, not stained, fixed in formalin/embedded in paraffin, mounted on slides (10 micron sections), as well as two serum samples in two 10-ml tubes and two blood samples (see appendix X);
• unresectable metastatic (stage IV or IIIB malignant pleural effusion) NSCLC;
• WHO performance status < 2;

• Adequate bone marrow, hepatic and renal functions, assessed during the previous 14 days, that should be shown by the following characteristics:

  • hemoglobin > or = 10g/dl and no blood cell transfusion within the previous 2 weeks;
  • absolute neutrophil count > 2.0 10^9 cells/l;
  • platelet count > or = 100.10^9 cells/l;
  • no evidence of myelodysplastic syndrome or abnormal bone marrow reserve;
  • creatinine < or = 1.5 x UNL or creatinine clearance > or = 60 ml/min (real or calculated);
  • total bilirubin < or = UNL;
  • ASAT (SGOT) and/or ALAT (SGPT) < or = 1.5 x UNL;
  • alkaline phosphatases < or = 5 x UNL;
  • serum calcium < or = 1.1 x UNL;
• at least one measurable lesion;
• previous surgery intervention (more than 30 days before inclusion in the study) is allowed but metastatic disease must be demonstrated;

• previous radiotherapy is allowed if:

  • less or equal to 10% of bone marrow has been irradiated
  • end of radiotherapy 21 days or more prior to inclusion in the study;
  • patient has fully recovered from all toxic effects;
  • at least one of the measurable target lesions for evaluation of tumor response has not been irradiated;
• the patient must be accessible for treatment and follow-up. The patient entered into this trial must be treated and followed up at the participating center;
• life expectancy > or = 12 weeks;
• The initial diagnostic procedures should be performed during the 4 weeks prior to the randomization.

Exclusion Criteria:

• pregnant or lactating women (women of childbearing potential must use adequate contraception);
• prior systemic chemotherapy or immunotherapy for NSCLC, even as neoadjuvant or adjuvant therapy;
• prior malignancies, except cured non-melanoma skin cancer, curatively treated in situ carcinoma of the cervix or other cancer curatively treated and with non-evidence of disease for at least 5 years;
• history or clinical symptomatic brain or leptomeningeal metastases;
• current peripheral neuropathy and neurohearing > or = NCIC-CTG grade 2 except if due to trauma;

• other serious illness or medical condition, including:

  • congestive heart disease; prior myocardial infarction within 6 months;
  • history of significant neurologic or psychiatric disorders that would inhibit their understanding and giving of informed consent;
  • infection requiring I.V. antibiotics and tuberculosis under treatment ongoing at study entry;
  • untreated superior vena cava syndrome;
  • active peptic ulcer; unstable diabetes mellitus or other contraindication to high dose corticotherapy such as herpes, herpes zoster, cirrhosis;
• hypercalcemia requiring therapy;
• preexisting ascitis and/or clinical significant pericardial effusion;
• patients whose lesion(s) are assessable only by radionuclide scan;
• history of allergy to drugs containing the excipient TWEEN 80®;
• concurrent treatment with other investigational drugs;
• participation in a clinical trial of one or more investigational agents (i.e. antibiotic) or devices within 30 days of study entry.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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: 1	Drug: docetaxel/gemcitabine
Active Comparator: 2	Drug: Docetaxel/DDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall response rate (complete plus partial responses) between the genotypic group and the control group using an intent-to-treat analysis.

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to treatment failure and survival	calculated from the registration date until progression or death, respectively
Clinical and laboratory toxicities graded according to NCIC-CTG Expanded Common Toxicity Criteria.	before each cycle
Adverse events not reported in NCIC-CTG Expanded Common Toxicity Criteria will be graded as mild, moderate, severe, and life threatening.	Throughout the study

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): December 7, 2009
• Last Update Submitted That Met QC Criteria: December 4, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gemcitabine; Docetaxel
• Other Study ID Numbers: TAX_ES1_302