Study of Rofecoxib and Prolonged Constant Infusion of Gemcitabine in the Polychemotherapy Treatment of Advanced NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the tolerability and efficacy of the addition of rofecoxib to first-line chemotherapy, and to evaluate the efficacy of prolonged continuous infusion of gemcitabine in combination with cisplatin in the treatment of patients affected by advanced non-small cell lung cancer.

Detailed Description
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The primary end-points of the GECO study To evaluate the tolerability of three innovative schedules of treatment for advanced NSCLC To evaluate the efficacy of the addition of rofecoxib to first-line chemotherapy in the treatment of patients affected by advanced NSCLC To evaluate the efficacy of prolonged continuous infusion (p.c.i.) of gemcitabine, with the fixed infusion rate of 10 mg/sqm/minute) versus the standard administration in 30 minutes, in combination with cisplatin, in the treatment of patients affected by advanced NSCLC Four treatment arms are planned. ARM A standard treatment : cisplatin + gemcitabine ARM B cisplatin + gemcitabine + rofecoxib ARM C cisplatin + p.c.i. gemcitabine (10 mg/sqm/minute) ARM D cisplatin + p.c.i gemcitabine (10 mg/sqm/minute) + rofecoxib The phase II part of the study for experimental arms B, C and D will be conducted to evaluate tolerability in the three treatment arms. The phase III study for efficacy has been designed according to a factorial 2x2 model with the planned comparison of The efficacy of rofecoxib: A + C (arms without rofecoxib) vs B+D (arms with rofecoxib) The efficacy of p.c.i. gemcitabine: A + B (arms with standard infusion of gemcitabine) vs C+ D (arms with p.c.i gemcitabine)

Official Title
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Phase II-III, Factorial Multicenter Randomized Trial Evaluating the Addition of Rofecoxib to Polycht With Cispatin and Gemcitabine and Fixed Dose Rate Infusion of Gem in Association With Cisplatin in 1st-line for Advanced NSCLC

Conditions
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Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: gemcitabine
* Drug: prolonged continuous infusion gemcitabine
* Drug: cisplatin
* Drug: rofecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologic or histologic diagnosis of non-small cell lung cancer Disease stage IIIB or IV Age less than 70 years ECOG performance status 2 or less Patients with cerebral metastases are permitted if they are asymptomatic and do not require radiation therapy concomitant with chemotherapy Negative history of allergy to non-steroidal anti-inflammatory and/or sulphonamide drugs Patients previously treated with radiation therapy are permitted if at least 4 weeks have passed since last therapy Written informed consent Exclusion Criteria: Previous chemotherapy Previous or concomitant malignant neoplasm (excluding adequately treated baso or spinocellular skin carcinoma or carcinoma in situ of the cervix) Neutrophil < 2000/mm3, platelets < 100,000/mm3, haemoglobin < 10 g/dl Creatinine > 1.25 x the upper normal limits GOT and/or GPT and/or Bilirubin > 1.25 the upper normal limits in absence of hepatic metastases GOT and/or GPT and/or Bilirubin > 2.5 the upper normal limits in presence of hepatic metastases Any concomitant pathology that would, in the investigator's opinion, contraindicate the use of the drugs in this study Inability to comply with follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: cisplatino plus gemcitabine<br>Gemcitabina 1200 mg/m2 infusion of 30 minutes at day 1, 8 + cisplatin 80 mg/m² day 1, every 3 weeks for 6 cycles. | Drug: gemcitabine<br> <br> Drug: cisplatin<br> <br> |
| Experimental: cisplatino plus gemcitabine plus rofecoxib<br>Gemcitabina 1200 mg/m2 infusion of 30 minutes at day 1, 8 + cisplatin 80 mg/m² day 1, every 3 weeks + rofecoxib 50 mg/die per os until progression of disease. | Drug: gemcitabine<br> <br> Drug: cisplatin<br> <br> Drug: rofecoxib<br> <br> |
| Experimental: cisplatino plus gemcitabine 10 mg/m2/min<br>Gemcitabina 1200 mg/m2 infusion of 120 minutes at day 1, 8 + cisplatin 80 mg/m² day 1, every 3 weeks for 6 cycles. | Drug: prolonged continuous infusion gemcitabine<br> <br> Drug: cisplatin<br> <br> |
| Experimental: cisplatino plus gemcitabine 10 mg/m2/min plus rofecoxib<br>Gemcitabina 1200 mg/m2 infusion of 120 minutes at day 1, 8 + cisplatin 80 mg/m² day 1, every 3 weeks + rofecoxib 50 mg/die per os until progression of disease. | Drug: prolonged continuous infusion gemcitabine<br> <br> Drug: cisplatin<br> <br> Drug: rofecoxib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the tolerability of three experimental treatment schedules | adverse events according to CTCAE criteria | at the end of each cycle of chemotherapy (every 3 weeks) until 21 days after the last treatment administrationministration | 
| To evaluate the efficacy of the addition of rofecoxib to first-line chemotherapy | response rate according to RECIST criteria | at the end of cycle 3 and cycle 6 until the date of first documented PD (up to 1 year). | 
| To evaluate the efficacy of prolonged continuous infusion (p.c.i.) of gemcitabine vs standard infusion, in combination with cisplatin | response rate according to RECIST criteria | at the end of cycle 3 and cycle 6 until the date of first documented PD (up to 1 year). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prolonged continuous infusion, Cox-2 inhibitors