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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: gemcitabine; Drug: prolonged continuous infusion gemcitabine; Drug: rofecoxib

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • Ospedale L. Sacco
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
  • Napoli, Italy
    • Second University of Naples
  • Pietre Ligure, Italy
    • Ospedale Santa Corona
  • Roma, Italy, 00144
    • Istituto Regina Elena, Divisione di Oncologia Medica
  • Roma, Italy, 00186
    • Ospedale S. Giovanni Calibita Gatebenefratelli
  • Rome, Italy
    • Ospedale San Camillo - Forlanini
  • Saronno, Italy
    • Azienda Ospedaliera Di Busto Arsizio
  • AV
    • Monteforte Irpino, AV, Italy, 83024
      • Azienda Ospedaliera S. Giuseppe Moscati, U.O. di Oncologia Medica
  • BA
    • Acquaviva delle Fonti, BA, Italy, 70021
      • Ospedale Regionale Miulli, Divisione Medicina Interna Sezione Oncologica
    • Bari, BA, Italy, 70126
      • IRCCS Oncologico Bari, Oncologia Medica
    • Bari, BA, Italy, 70126
      • Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale
  • CA
    • Cagliari, CA, Italy, 09042
      • Policlinico Universitario, Oncologia Medica II
  • CB
    • Campobasso, CB, Italy, 86100
      • Ospedale A. cardarelli
  • CS
    • Cosenza, CS, Italy, 87100
      • Ospedale Mariano Santo, U.O. di Oncologia Medica
  • FR
    • Frosinone, FR, Italy, 03031
      • Ospedale Umberto di Frosinone
  • MI
    • Legnano, MI, Italy
      • Ospedale Civile di Legnano
    • Milano, MI, Italy, 20142
      • Ospedale S. Paolo
  • PA
    • Palermo, PA, Italy, 90100
      • Policlinico Universitario P. Giaccone
    • Palermo, PA, Italy, 90146
      • Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
  • PD
    • Padova, PD, Italy
      • Istituto Oncologico Veneto
  • SA
    • Nocera Inferiore, SA, Italy, 84014
      • Ospedale Civile Umberto I, Day Hospital Oncoematologico
  • VE
    • Noale, VE, Italy, 30033
      • Divisione di Oncologia Medica, U.S.L.L. 13
  • VI
    • Vicenza, VI, Italy, 36100
      • Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cisplatino plus gemcitabine; 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: cisplatin; Drug: gemcitabine
Experimental: cisplatino plus gemcitabine plus rofecoxib; 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: cisplatin; Drug: gemcitabine; Drug: rofecoxib
Experimental: cisplatino plus gemcitabine 10 mg/m2/min; 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: cisplatin; Drug: prolonged continuous infusion gemcitabine
Experimental: cisplatino plus gemcitabine 10 mg/m2/min plus rofecoxib; 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: cisplatin; Drug: prolonged continuous infusion gemcitabine; Drug: rofecoxib

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples
• Investigators: Principal Investigator: Cesare Gridelli, M.D., San Giuseppe Moscati Hospital, Avellino, Italy; Principal Investigator: Francesco Perrone, M.D., Ph.D., National Cancer Institute Naples, Italy

Publications and helpful links

General Publications

• Gridelli C, Gallo C, Ceribelli A, Gebbia V, Gamucci T, Ciardiello F, Carozza F, Favaretto A, Daniele B, Galetta D, Barbera S, Rosetti F, Rossi A, Maione P, Cognetti F, Testa A, Di Maio M, Morabito A, Perrone F; GECO investigators. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol. 2007 Jun;8(6):500-12. doi: 10.1016/S1470-2045(07)70146-8.
• Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: October 10, 2006
• First Submitted That Met QC Criteria: October 10, 2006
• First Posted (Estimate): October 11, 2006

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: prolonged continuous infusion; Cox-2 inhibitors
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cyclooxygenase 2 Inhibitors; Gemcitabine; Rofecoxib
• Other Study ID Numbers: GECO