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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by National Cancer Institute, Naples
Information provided by (Responsible Party):
National Cancer Institute, Naples Identifier:
First received: July 23, 2012
Last updated: November 25, 2015
Last verified: November 2015
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.

Condition Intervention Phase
Non-small Cell Lung Cancer Metastatic
Non-small Cell Lung Cancer Stage IIIB
Drug: Gemcitabine
Drug: Pemetrexed
Drug: Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:

Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • overall survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    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)

Secondary Outcome Measures:
  • worst grade toxicity per patient [ Time Frame: evaluated at end of each 3 week cycle of chemotherapy up to 18 weeks ] [ Designated as safety issue: Yes ]
    according to Common Toxicity Criteria for Adverse Events v. 4.03

  • progression free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • changes in quality of life [ Time Frame: baseline and up to 18 weeks ] [ Designated as safety issue: No ]
  • objective response [ Time Frame: after 9 and 18 weeks of therapy ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • identification of patient and lesion specific prognostic factors [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • identification of patient and lesion specific factors predictive of chemotherapy efficacy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 550
Study Start Date: July 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: Gemcitabine
Single agent gemcitabine dose 1200 mg/m2 days 1 and 8, every 3 weeks
Drug: Gemcitabine
Experimental: B: Gemcitabine + Cisplatin
Gemcitabine dose 1000 mg/m2 days 1 and 8, every 3 weeks
Drug: Gemcitabine Drug: Cisplatin
60 mg/m2 day 1 every 3 weeks
Active Comparator: C: Pemetrexed Drug: Pemetrexed
500 mg/m2 day 1 every 3 weeks
Experimental: D: Pemetrexed + Cisplatin Drug: Pemetrexed
500 mg/m2 day 1 every 3 weeks
Drug: Cisplatin
60 mg/m2 day 1 every 3 weeks


Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01656551

Contact: Francesco Perrone, M.D., Ph.D. +39 081 5903571
Contact: Maria Carmela Piccirillo, M.D. +39 081 5903681

  Show 49 Study Locations
Sponsors and Collaborators
National Cancer Institute, Naples
Principal Investigator: 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
  More Information

Responsible Party: National Cancer Institute, Naples Identifier: NCT01656551     History of Changes
Other Study ID Numbers: MILES-4  2012-000164-25 
Study First Received: July 23, 2012
Last Updated: November 25, 2015
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on May 04, 2016