MILES-4: Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer

NCT01656551 | Unknown Phase 3

• 2 other identifiers: MILES-42012-000164-25
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 48

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.

Conditions

Non-small Cell Lung Cancer Metastatic; Non-small Cell Lung Cancer Stage IIIB

Keywords

elderly; chemotherapy

Outcome Measures

Primary Outcomes (1)

• overall survival

  factorial design with two comparisons: single agent chemotherapy versus chemotherapy plus cisplatin (Arms A+C versus Arms B + D), and gemcitabine versus pemetrexed (Arms A+B versus Arms C+D)

  one year

Secondary Outcomes (4)

• worst grade toxicity per patient

  evaluated at end of each 3 week cycle of chemotherapy up to 18 weeks

• progression free survival

  6 months

• changes in quality of life

  baseline and up to 18 weeks

• objective response

  after 9 and 18 weeks of therapy

Other Outcomes (2)

• identification of patient and lesion specific prognostic factors

  2 years

• identification of patient and lesion specific factors predictive of chemotherapy efficacy

  2 years

Study Arms (4)

A: Gemcitabine

ACTIVE COMPARATOR

Single agent gemcitabine dose 1200 mg/m2 days 1 and 8, every 3 weeks

Drug: Gemcitabine

B: Gemcitabine + Cisplatin

EXPERIMENTAL

Gemcitabine dose 1000 mg/m2 days 1 and 8, every 3 weeks

Drug: Gemcitabine; Drug: Cisplatin

C: Pemetrexed

ACTIVE COMPARATOR

Drug: Pemetrexed

D: Pemetrexed + Cisplatin

EXPERIMENTAL

Drug: Pemetrexed; Drug: Cisplatin

Interventions

Gemcitabine DRUG

A: Gemcitabine; B: Gemcitabine + Cisplatin

Pemetrexed DRUG

500 mg/m2 day 1 every 3 weeks

C: Pemetrexed; D: Pemetrexed + Cisplatin

Cisplatin DRUG

60 mg/m2 day 1 every 3 weeks

B: Gemcitabine + Cisplatin; D: Pemetrexed + Cisplatin

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (48)

Ospedale San Lazzaro

Alba, Italy

Location

Ospedali Riunit Umberto I-Lancisi-Salesi

Ancona, Italy

Location

Oncologia Universitaria degli Studi di Roma

Aprilia, Italy

Location

Ospedale Cardinal Massaia

Asti, Italy

Location

S. Giuseppe Moscati

Avellino, Italy

Location

Ospedale Senatore Antonio Perrino

Brindisi, Italy

Location

Univeristaria Policlinico Monserrato di Cagliari

Cagliari, Italy

Location

Ospedale A. cardarelli

Campobasso, Italy

Location

U.L.S.S. 15 Veneto

Camposampiero, Italy

Location

Ospedale Ramazzini di Carpi

Carpi, Italy

Location

Azienda Ospedaliera Garibalda Nesimadi Catania

Catania, Italy

Location

Policlinico vittorio Emanuele

Catania, Italy

Location

Ospedale della Madonna della Navicella

Chioggia, Italy

Location

Ospedale Civile di Faenza

Faenza, Italy

Location

Ospedale Fabrizio Spaziani

Frosinone, Italy

Location

IRCCS AOU San Martino IST Genova

Genova, Italy

Location

Ospedale Villa Scassi

Genova, Italy

Location

Azienda Ospedaliera Vito Fazzi

Lecce, Italy

Location

Ospedale Civile di Legnano

Legnano, Italy

Location

Ospedale Umberto I

Lugo, Italy

Location

IRCCS-Meldola

Meldola, Italy

Location

Ospedale L. Sacco Polo Universitario

Milan, Italy

Location

Ospedale S. Paolo

Milan, Italy

Location

U.L.S.S. 13

Mirano, Italy

Location

H San Gerardo

Monza, Italy

Location

A.O.U. Federico II

Napoli, Italy

Location

Istituto Nazionale dei Tumori

Napoli, Italy

Location

Ospedale Cardirelli

Napoli, Italy

Location

Seconda Università di Napoli

Napoli, Italy

Location

Istituto Sacro Cuore Don Calabria

Negrar, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Ospedale Civile Umberto I

Pagani, Italy

Location

Azienda Ospedaleira Ospedali Riuniti Villa Sofia Cervello

Palermo, Italy

Location

Casa di cura La Maddalena

Palermo, Italy

Location

Fondazione Salvatore Maugeri

Pavia, Italy

Location

A.O. San Carlo

Potenza, Italy

Location

Irccs - Crob

Rionero in Vulture, Italy

Location

AO San Camillo Forlanini

Roma, Italy

Location

Campus Biomedico

Roma, Italy

Location

Ospedale S. Giovanni Calibita Fatebenfratelli

Roma, Italy

Location

Ospedale Guglielmo da Saliceto-USL di Piacenza

Saliceto, Italy

Location

Oncologia IRCCS - Casa Sollievo Sofferenza

San Giovanni Rotondo, Italy

Location

A.O. di Busto Arsizio

Saronno, Italy

Location

Ospedale di Sondrio

Sondrio, Italy

Location

Ospedale SS. Trinità

Sora, Italy

Location

Ospedale S. Andrea

Vercelli, Italy

Location

Ospedale S. Bortolo

Vicenza, Italy

Location

ASL Viterbo Ospedale Belcolle

Viterbo, Italy

Location

Related Publications (1)

• 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.

  PMID: 30028656 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Cesare Gridelli, M.D.

  S.G. Moscati Hopital, Avellino, Italy, Division of Medical Oncology

  PRINCIPAL INVESTIGATOR

• Francesco Perrone, M.D., Ph.D

  National Cancer Institute Naples, Italy; Director Clinical Trials Unit

  PRINCIPAL INVESTIGATOR

• Ciro Gallo, M.D., Ph.D

  Second University of Naples, Italy; Chair of Medical Statistics

  PRINCIPAL INVESTIGATOR

• Massimo Di Maio, M.D.

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: August 3, 2012
• Study Start: August 1, 2012
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

IT (48)