Clinical trial NCT00385606: Study of Rofecoxib and Prolonged Constant Infusion of Gemcitabine in the Polychemotherapy Treatment of Advanced NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Advanced Non-small Cell Lung Cancer
Keywords: prolonged continuous infusion
Cox-2 inhibitors
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2006-10-11
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the tolerability of three experimental treatment schedules
timeFrame: at the end of each cycle of chemotherapy (every 3 weeks) until 21 days after the last treatment administrationministration
measure: To evaluate the efficacy of the addition of rofecoxib to first-line chemotherapy
timeFrame: at the end of cycle 3 and cycle 6 until the date of first documented PD (up to 1 year).
measure: To evaluate the efficacy of prolonged continuous infusion (p.c.i.) of gemcitabine vs standard infusion, in combination with cisplatin
timeFrame: at the end of cycle 3 and cycle 6 until the date of first documented PD (up to 1 year).
Secondary outcomes:
Other outcomes:
Locations:
city: Monteforte Irpino
country: Italy
facility: Azienda Ospedaliera S. Giuseppe Moscati, U.O. di Oncologia Medica
state: AV
city: Acquaviva delle Fonti
country: Italy
facility: Ospedale Regionale Miulli, Divisione Medicina Interna Sezione Oncologica
state: BA
city: Bari
country: Italy
facility: IRCCS Oncologico Bari, Oncologia Medica
state: BA
city: Bari
country: Italy
facility: Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale
state: BA
city: Cagliari
country: Italy
facility: Policlinico Universitario, Oncologia Medica II
state: CA
city: Campobasso
country: Italy
facility: Ospedale A. Cardarelli
state: CB
city: Cosenza
country: Italy
facility: Ospedale Mariano Santo, U.O. di Oncologia Medica
state: CS
city: Frosinone
country: Italy
facility: Ospedale Umberto di Frosinone
state: FR
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano
state: MI
city: Milano
country: Italy
facility: Ospedale S. Paolo
state: MI
city: Palermo
country: Italy
facility: Policlinico Universitario P. Giaccone
state: PA
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
state: PA
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
state: PD
city: Nocera Inferiore
country: Italy
facility: Ospedale Civile Umberto I, Day Hospital Oncoematologico
state: SA
city: Noale
country: Italy
facility: Divisione di Oncologia Medica, U.S.L.L. 13
state: VE
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica
state: VI
city: Milano
country: Italy
facility: Ospedale L. Sacco
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
city: Napoli
country: Italy
facility: Second University of Naples
city: Pietre Ligure
country: Italy
facility: Ospedale Santa Corona
city: Roma
country: Italy
facility: Istituto Regina Elena, Divisione di Oncologia Medica
city: Roma
country: Italy
facility: Ospedale S. Giovanni Calibita Gatebenefratelli
city: Rome
country: Italy
facility: Ospedale San Camillo - Forlanini
city: Saronno
country: Italy
facility: Azienda Ospedaliera Di Busto Arsizio
Study officials:
affiliation: San Giuseppe Moscati Hospital, Avellino, Italy
name: Cesare Gridelli, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute Naples, Italy
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.