Clinical trial NCT00786331: Pemetrexed +/- Carboplatin as Second Line Treatment in NSCLC
Official title: Randomized Phase II Study of Pemetrexed Versus Pemetrexed and Carboplatin as Second Line Chemotherapy in Advanced Non-small-cell Lung Cancer (NSCLC).
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Non-Small Cell Lung Cancer
Keywords: second line treatment
pemetrexed
carboplatin
Lead sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sponsor class: OTHER
First posted: 2008-11-06
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC.

Detailed description: In spite of the superiority of single agent over best supportive care in second-line NSCLC, the prognosis of these patients remains poor with a median survival of 6-7 months, justifying the evaluation of new regimens in this setting. An open question in the second-line treatment of NSCLC remains the possible superiority of combination chemotherapy over single agent, as it has been clearly demonstrated in first-line. Particularly, the addition of platinum to either docetaxel or pemetrexed should be further investigated especially in patients with prior response/stable disease to platinum-based first-line chemotherapy. Pemetrexed has shown anti-tumor activity in combination with other chemotherapy agents, including gemcitabine, vinorelbine, taxanes, cisplatin and carboplatin. In this multicenter, open label, randomized phase II trial, pemetrexed 500 mg/m2 and carboplatin AUC 5 will be administered on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses in the experimental arm. The control arm will be pemetrexed as single agent at 500 mg/m2 on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses.

Eligibility criteria: Inclusion Criteria:

* written informed consent
* Histologically or cytologically confirmed non-small-cell lung cancer
* Unresectable stage IIIB, stage IV and unresectable local relapse or metastatic disease, with evidence of disease progression after first line chemotherapy which should have included a platinum agent.
* ECOG performance status lower than or equal to 2
* Adequate hematological, hepatic and renal functions
* Life expectancy greater than or equal to 12 weeks
* Prior treatment with only 1 chemotherapy regimen for the treatment of advanced disease which should have included a platinum agent
* At baseline, presence of at least one measurable target lesion as per RECIST criteria

Exclusion Criteria:

* Prior treatment with pemetrexed.
* Patients who are pregnant or lactating
* Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled.
* Symptomatic brain metastases
* History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
* Concomitant treatment with any other anticancer drug.

Primary outcomes:
measure: To compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC
timeFrame: 36 months
Secondary outcomes:
measure: To assess differences in terms of response rate between the combination pemetrexed-carboplatin and pemetrexed alone.
timeFrame: 3 months
measure: To assess differences in terms of duration of response between the combination pemetrexed-carboplatin and pemetrexed alone.
timeFrame: 36 months
measure: To assess differences in terms of toxicity between the combination pemetrexed-carboplatin and pemetrexed alone.
timeFrame: 3 months
measure: To assess differences in terms of survival between the combination pemetrexed-carboplatin and pemetrexed alone.
timeFrame: 36 months
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria Umberto I, Clinica di Oncologia Medica
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti di Bergamo, UO di Oncologia Medica
city: Cremona
country: Italy
facility: Azienda Istituti Ospitalieri di Cremona, UO di Oncologia Medica
city: Cuneo
country: Italy
facility: Azienda Sanitaria Ospedaliera S. Croce e Carle, UO di Oncologia Medica
city: Fano, PU
country: Italy
facility: Ospedale S. Croce, U.O. di Oncologia Medica
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi, UO di Oncologia Medica
city: Genova
country: Italy
facility: EO Ospedali Galliera, SC Oncologia Medica
city: Lido di Camaiore, LU
country: Italy
facility: Ospedale Versilia, UO di Oncologia Medica
city: Livorno
country: Italy
facility: USL 6, Presidio Ospedaliero di Livorno, U.O. di Oncologia MedicaAzienda
city: Meldola, FC
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST, Oncologia Medica
city: Milano
country: Italy
facility: Istituto Nazionale Tumori, SC di Oncologia 2
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena-Policlinico, U.O. di Oncologia Medica ed Ematologia
city: Monza, MI
country: Italy
facility: AO S. Gerardo, Nuovo Ospedale S. Gerardo-settore A, Oncologia Medica
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica
city: Perugia
country: Italy
facility: Ospedale Silvestrini, S.C. di Oncologia Medica
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova, UO di Oncologia Medica
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Camillo-Forlanini, U.O. di Oncologia Medica
city: Sassari
country: Italy
facility: Ospedale SS. Annunziata, UO di Oncologia Medica
city: Torino
country: Italy
facility: Azienda Sanitaria Ospedaliera Molinette, U.O. di Oncologia Medica
city: Treviglio, BG
country: Italy
facility: P.O. Treviglio-Caravaggio, U.O. di Oncologia Medica
city: Verona
country: Italy
facility: Policlinico "G. B. Rossi"-Borgo Roma, U.O. di Oncologia Medica Clinicizzata
Study officials:
affiliation: Gruppo Oncologico Italiano di Ricerca Clinica
name: Andrea Ardizzoni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Kruijsdijk RC, Visseren FL, Boni L, Groen HJ, Dingemans AM, Aerts JG, van der Graaf Y, Ardizzoni A, Smit EF. Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer: treating the right patients based on individualized treatment effect prediction. Ann Oncol. 2016 Jul;27(7):1280-6. doi: 10.1093/annonc/mdw154. Epub 2016 Apr 6.
citation: Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crino L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. doi: 10.1200/JCO.2012.43.6758. Epub 2012 Oct 29.