Clinical trial NCT01656551: MILES-4: Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer
Official title: A Factorial Study Comparing Pemetrexed With Gemcitabine and Testing the Efficacy of the Addition of Cisplatin in Elderly Patients With Non Squamous Advanced, Metastatic or Recurrent NSCLC.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer Metastatic
Non-small Cell Lung Cancer Stage IIIB
Keywords: elderly
chemotherapy
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2012-08-03
Enrollment: 232
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purposes of this study are to test whether the addition of cisplatin to single agent chemotherapy (either gemcitabine or pemetrexed) prolongs survival in elderly patients with non squamous non small cell lung cancer (NSCLC), and to test whether pemetrexed prolongs survival as compared to gemcitabine in elderly patients with non squamous NSCLC.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of cytologically or histologically confirmed non-small cell lung cancer.
* Non squamous tumor type (including those with a non-specified tumor type).
* Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes) according to TNM VII edition.
* Both patients at first diagnosis or those with disease recurrence after former surgery are eligible.
* At least one target or non-target lesion according to RECIST revised version 1.1.
* Male or female \> or = 70 years of age.
* ECOG PS 0 or 1.
* Life expectancy \> 3 months.
* Neutrophils \> or = 1500 mm3, platelets \> or = 100000 mm3, and haemoglobin \> or = 9 g/dL.
* Bilirubin level either normal or \< 1.5 x ULN.
* AST (SGOT) and ALT (SGPT) \< or = 2.5 x ULN (\< or = 5 x ULN if liver metastasis are present).
* Serum creatinine \< 1.5 x ULN.
* Signed written informed consent.

Exclusion Criteria:

* Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease. Prior surgery and/or localised irradiation is permitted. Prior adjuvant chemotherapy is permitted if it did not contain gemcitabine and pemetrexed and if at least 6 months elapsed from the end of adjuvant chemotherapy.
* Any unstable systemic disease (including active infections, significant cardiovascular disease or myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medications or render the patient at high risk from treatment complications.
* Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA).
* Patients with symptomatic brain metastasis or spinal cord compression that has not yet been treated with surgery and/or radiation; patients with CNS metastases or spinal cord compression previously treated with surgery and/or radiation are eligible if they are asymptomatic and do not require steroids (anti-seizure medications are allowed).
* Known or suspected hypersensitivity to any of the study drugs

Primary outcomes:
measure: overall survival
timeFrame: one year
Secondary outcomes:
measure: worst grade toxicity per patient
timeFrame: evaluated at end of each 3 week cycle of chemotherapy up to 18 weeks
measure: progression free survival
timeFrame: 6 months
measure: changes in quality of life
timeFrame: baseline and up to 18 weeks
measure: objective response
timeFrame: after 9 and 18 weeks of therapy
Other outcomes:
measure: identification of patient and lesion specific prognostic factors
timeFrame: 2 years
measure: identification of patient and lesion specific factors predictive of chemotherapy efficacy
timeFrame: 2 years
Locations:
city: Alba
country: Italy
facility: Ospedale San Lazzaro
city: Ancona
country: Italy
facility: Ospedali Riunit Umberto I-Lancisi-Salesi
city: Aprilia
country: Italy
facility: Oncologia Universitaria degli Studi di Roma
city: Asti
country: Italy
facility: Ospedale Cardinal Massaia
city: Avellino
country: Italy
facility: S. Giuseppe Moscati
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Cagliari
country: Italy
facility: Univeristaria Policlinico Monserrato di Cagliari
city: Campobasso
country: Italy
facility: Ospedale A. cardarelli
city: Camposampiero
country: Italy
facility: U.L.S.S. 15 Veneto
city: Carpi
country: Italy
facility: Ospedale Ramazzini di Carpi
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibalda Nesimadi Catania
city: Catania
country: Italy
facility: Policlinico vittorio Emanuele
city: Chioggia
country: Italy
facility: Ospedale della Madonna della Navicella
city: Faenza
country: Italy
facility: Ospedale Civile di Faenza
city: Frosinone
country: Italy
facility: Ospedale Fabrizio Spaziani
city: Genova
country: Italy
facility: IRCCS AOU San Martino IST Genova
city: Genova
country: Italy
facility: Ospedale Villa Scassi
city: Lecce
country: Italy
facility: Azienda Ospedaliera Vito Fazzi
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano
city: Lugo
country: Italy
facility: Ospedale Umberto I
city: Meldola
country: Italy
facility: IRCCS-Meldola
city: Milano
country: Italy
facility: Ospedale L. Sacco Polo Universitario
city: Milano
country: Italy
facility: Ospedale S. Paolo
city: Mirano
country: Italy
facility: U.L.S.S. 13
city: Monza
country: Italy
facility: H San Gerardo
city: Napoli
country: Italy
facility: A.O.U. Federico II
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Ospedale Cardirelli
city: Napoli
country: Italy
facility: Seconda Università di Napoli
city: Negrar
country: Italy
facility: Istituto Sacro Cuore Don Calabria
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Pagani
country: Italy
facility: Ospedale Civile Umberto I
city: Palermo
country: Italy
facility: Azienda Ospedaleira Ospedali Riuniti Villa Sofia Cervello
city: Palermo
country: Italy
facility: Casa di cura La Maddalena
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Potenza
country: Italy
facility: A.O. San Carlo
city: Rionero in Vulture
country: Italy
facility: Irccs - Crob
city: Roma
country: Italy
facility: AO San Camillo Forlanini
city: Roma
country: Italy
facility: Campus Biomedico
city: Roma
country: Italy
facility: Ospedale S. Giovanni Calibita Fatebenfratelli
city: Saliceto
country: Italy
facility: Ospedale Guglielmo da Saliceto-USL di Piacenza
city: San Giovanni Rotondo
country: Italy
facility: Oncologia IRCCS - Casa Sollievo Sofferenza
city: Saronno
country: Italy
facility: A.O. di Busto Arsizio
city: Sondrio
country: Italy
facility: Ospedale di Sondrio
city: Sora
country: Italy
facility: Ospedale SS. Trinità
city: Vercelli
country: Italy
facility: Ospedale S. Andrea
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo
city: Viterbo
country: Italy
facility: ASL Viterbo Ospedale Belcolle
Study officials:
affiliation: S.G. Moscati Hopital, Avellino, Italy, Division of Medical Oncology
name: Cesare Gridelli, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute Naples, Italy; Director Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Second University of Naples, Italy; Chair of Medical Statistics
name: Ciro Gallo, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Massimo Di Maio, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. doi: 10.1200/JCO.2017.76.8390. Epub 2018 Jul 20.