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

Primary Purpose

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

Status
Active
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Gemcitabine
Pemetrexed
Cisplatin
Sponsored by
National Cancer Institute, Naples
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer Metastatic focused on measuring elderly, chemotherapy

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ospedale San Lazzaro
  • Ospedali Riunit Umberto I-Lancisi-Salesi
  • Oncologia Universitaria degli Studi di Roma
  • Ospedale Cardinal Massaia
  • S. Giuseppe Moscati
  • Ospedale Senatore Antonio Perrino
  • Univeristaria Policlinico Monserrato di Cagliari
  • Ospedale A. cardarelli
  • U.L.S.S. 15 Veneto
  • Ospedale Ramazzini di Carpi
  • Azienda Ospedaliera Garibalda Nesimadi Catania
  • Policlinico vittorio Emanuele
  • Ospedale della Madonna della Navicella
  • Ospedale Civile di Faenza
  • Ospedale Fabrizio Spaziani
  • IRCCS AOU San Martino IST Genova
  • Ospedale Villa Scassi
  • Azienda Ospedaliera Vito Fazzi
  • Ospedale Civile di Legnano
  • Ospedale Umberto I
  • IRCCS-Meldola
  • Ospedale L. Sacco Polo Universitario
  • Ospedale S. Paolo
  • U.L.S.S. 13
  • H San Gerardo
  • A.O.U. Federico II
  • Istituto Nazionale dei Tumori
  • Ospedale Cardirelli
  • Seconda Università di Napoli
  • Istituto Sacro Cuore Don Calabria
  • Istituto Oncologico Veneto
  • Ospedale Civile Umberto I
  • Azienda Ospedaleira Ospedali Riuniti Villa Sofia Cervello
  • Casa di cura La Maddalena
  • Fondazione Salvatore Maugeri
  • A.O. San Carlo
  • Irccs - Crob
  • AO San Camillo Forlanini
  • Campus Biomedico
  • Ospedale S. Giovanni Calibita Fatebenfratelli
  • Ospedale Guglielmo da Saliceto-USL di Piacenza
  • Oncologia IRCCS - Casa Sollievo Sofferenza
  • A.O. di Busto Arsizio
  • Ospedale di Sondrio
  • Ospedale SS. Trinità
  • Ospedale S. Andrea
  • Ospedale S. Bortolo
  • ASL Viterbo Ospedale Belcolle

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

A: Gemcitabine

B: Gemcitabine + Cisplatin

C: Pemetrexed

D: Pemetrexed + Cisplatin

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

worst grade toxicity per patient
according to Common Toxicity Criteria for Adverse Events v. 4.03
progression free survival
changes in quality of life
objective response

Full Information

First Posted
July 23, 2012
Last Updated
March 23, 2023
Sponsor
National Cancer Institute, Naples
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1. Study Identification

Unique Protocol Identification Number
NCT01656551
Brief Title
MILES-4: Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer
Acronym
MILES-4
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2012 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute, Naples

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Metastatic, Non-small Cell Lung Cancer Stage IIIB
Keywords
elderly, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
232 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Gemcitabine
Arm Type
Active Comparator
Arm Description
Single agent gemcitabine dose 1200 mg/m2 days 1 and 8, every 3 weeks
Arm Title
B: Gemcitabine + Cisplatin
Arm Type
Experimental
Arm Description
Gemcitabine dose 1000 mg/m2 days 1 and 8, every 3 weeks
Arm Title
C: Pemetrexed
Arm Type
Active Comparator
Arm Title
D: Pemetrexed + Cisplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
500 mg/m2 day 1 every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
60 mg/m2 day 1 every 3 weeks
Primary Outcome Measure Information:
Title
overall survival
Description
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)
Time Frame
one year
Secondary Outcome Measure Information:
Title
worst grade toxicity per patient
Description
according to Common Toxicity Criteria for Adverse Events v. 4.03
Time Frame
evaluated at end of each 3 week cycle of chemotherapy up to 18 weeks
Title
progression free survival
Time Frame
6 months
Title
changes in quality of life
Time Frame
baseline and up to 18 weeks
Title
objective response
Time Frame
after 9 and 18 weeks of therapy
Other Pre-specified Outcome Measures:
Title
identification of patient and lesion specific prognostic factors
Time Frame
2 years
Title
identification of patient and lesion specific factors predictive of chemotherapy efficacy
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cesare Gridelli, M.D.
Organizational Affiliation
S.G. Moscati Hopital, Avellino, Italy, Division of Medical Oncology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francesco Perrone, M.D., Ph.D
Organizational Affiliation
National Cancer Institute Naples, Italy; Director Clinical Trials Unit
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ciro Gallo, M.D., Ph.D
Organizational Affiliation
Second University of Naples, Italy; Chair of Medical Statistics
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Massimo Di Maio, M.D.
Organizational Affiliation
National Cancer Institute, Naples
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ospedale San Lazzaro
City
Alba
Country
Italy
Facility Name
Ospedali Riunit Umberto I-Lancisi-Salesi
City
Ancona
Country
Italy
Facility Name
Oncologia Universitaria degli Studi di Roma
City
Aprilia
Country
Italy
Facility Name
Ospedale Cardinal Massaia
City
Asti
Country
Italy
Facility Name
S. Giuseppe Moscati
City
Avellino
Country
Italy
Facility Name
Ospedale Senatore Antonio Perrino
City
Brindisi
Country
Italy
Facility Name
Univeristaria Policlinico Monserrato di Cagliari
City
Cagliari
Country
Italy
Facility Name
Ospedale A. cardarelli
City
Campobasso
Country
Italy
Facility Name
U.L.S.S. 15 Veneto
City
Camposampiero
Country
Italy
Facility Name
Ospedale Ramazzini di Carpi
City
Carpi
Country
Italy
Facility Name
Azienda Ospedaliera Garibalda Nesimadi Catania
City
Catania
Country
Italy
Facility Name
Policlinico vittorio Emanuele
City
Catania
Country
Italy
Facility Name
Ospedale della Madonna della Navicella
City
Chioggia
Country
Italy
Facility Name
Ospedale Civile di Faenza
City
Faenza
Country
Italy
Facility Name
Ospedale Fabrizio Spaziani
City
Frosinone
Country
Italy
Facility Name
IRCCS AOU San Martino IST Genova
City
Genova
Country
Italy
Facility Name
Ospedale Villa Scassi
City
Genova
Country
Italy
Facility Name
Azienda Ospedaliera Vito Fazzi
City
Lecce
Country
Italy
Facility Name
Ospedale Civile di Legnano
City
Legnano
Country
Italy
Facility Name
Ospedale Umberto I
City
Lugo
Country
Italy
Facility Name
IRCCS-Meldola
City
Meldola
Country
Italy
Facility Name
Ospedale L. Sacco Polo Universitario
City
Milano
Country
Italy
Facility Name
Ospedale S. Paolo
City
Milano
Country
Italy
Facility Name
U.L.S.S. 13
City
Mirano
Country
Italy
Facility Name
H San Gerardo
City
Monza
Country
Italy
Facility Name
A.O.U. Federico II
City
Napoli
Country
Italy
Facility Name
Istituto Nazionale dei Tumori
City
Napoli
Country
Italy
Facility Name
Ospedale Cardirelli
City
Napoli
Country
Italy
Facility Name
Seconda Università di Napoli
City
Napoli
Country
Italy
Facility Name
Istituto Sacro Cuore Don Calabria
City
Negrar
Country
Italy
Facility Name
Istituto Oncologico Veneto
City
Padova
Country
Italy
Facility Name
Ospedale Civile Umberto I
City
Pagani
Country
Italy
Facility Name
Azienda Ospedaleira Ospedali Riuniti Villa Sofia Cervello
City
Palermo
Country
Italy
Facility Name
Casa di cura La Maddalena
City
Palermo
Country
Italy
Facility Name
Fondazione Salvatore Maugeri
City
Pavia
Country
Italy
Facility Name
A.O. San Carlo
City
Potenza
Country
Italy
Facility Name
Irccs - Crob
City
Rionero in Vulture
Country
Italy
Facility Name
AO San Camillo Forlanini
City
Roma
Country
Italy
Facility Name
Campus Biomedico
City
Roma
Country
Italy
Facility Name
Ospedale S. Giovanni Calibita Fatebenfratelli
City
Roma
Country
Italy
Facility Name
Ospedale Guglielmo da Saliceto-USL di Piacenza
City
Saliceto
Country
Italy
Facility Name
Oncologia IRCCS - Casa Sollievo Sofferenza
City
San Giovanni Rotondo
Country
Italy
Facility Name
A.O. di Busto Arsizio
City
Saronno
Country
Italy
Facility Name
Ospedale di Sondrio
City
Sondrio
Country
Italy
Facility Name
Ospedale SS. Trinità
City
Sora
Country
Italy
Facility Name
Ospedale S. Andrea
City
Vercelli
Country
Italy
Facility Name
Ospedale S. Bortolo
City
Vicenza
Country
Italy
Facility Name
ASL Viterbo Ospedale Belcolle
City
Viterbo
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
30028656
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.
Results Reference
derived

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

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