Pemetrexed +/- Carboplatin as Second Line Treatment in NSCLC

Randomized Phase II Study of Pemetrexed Versus Pemetrexed and Carboplatin as Second Line Chemotherapy in Advanced Non-small-cell Lung Cancer (NSCLC).

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Pemetrexed plus carboplatin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Luca Boni, MD; Phone Number: +39 0557947553; Email: bonil@aou-careggi.toscana.it

Study Locations

• Italy
  • Ancona, Italy, 60020
    • Active, not recruiting
    • Azienda Ospedaliero-Universitaria Umberto I, Clinica di Oncologia Medica
  • Bergamo, Italy, 24128
    • Recruiting
    • Azienda Ospedaliera Ospedali Riuniti di Bergamo, UO di Oncologia Medica
  • Cremona, Italy, 26100
    • Recruiting
    • Azienda Istituti Ospitalieri di Cremona, UO di Oncologia Medica
  • Cuneo, Italy, 12100
    • Recruiting
    • Azienda Sanitaria Ospedaliera S. Croce e Carle, UO di Oncologia Medica
  • Fano, PU, Italy, 61032
    • Recruiting
    • Ospedale S. Croce, U.O. di Oncologia Medica
  • Firenze, Italy, 50139
    • Recruiting
    • Azienda Ospedaliera Careggi, UO di Oncologia Medica
  • Genova, Italy, 16128
    • Recruiting
    • EO Ospedali Galliera, SC Oncologia Medica
  • Lido di Camaiore, LU, Italy, 55043
    • Recruiting
    • Ospedale Versilia, UO di Oncologia Medica
  • Livorno, Italy, 57122
    • Recruiting
    • USL 6, Presidio Ospedaliero di Livorno, U.O. di Oncologia MedicaAzienda
  • Meldola, FC, Italy, 47014
    • Recruiting
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST, Oncologia Medica
  • Milano, Italy, 20133
    • Recruiting
    • Istituto Nazionale Tumori, SC di Oncologia 2
    • Principal Investigator: Emilio Baietta, MD
  • Modena, Italy, 41100
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Modena-Policlinico, U.O. di Oncologia Medica ed Ematologia
  • Monza, MI, Italy, 20052
    • Not yet recruiting
    • AO S. Gerardo, Nuovo Ospedale S. Gerardo-settore A, Oncologia Medica
    • Principal Investigator: Paolo Bidoli, MD
  • Parma, Italy, 43100
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica
  • Perugia, Italy, 06156
    • Recruiting
    • Ospedale Silvestrini, S.C. di Oncologia Medica
    • Principal Investigator: Lucio Crinò, MD
  • Reggio Emilia, Italy, 42100
    • Recruiting
    • Arcispedale Santa Maria Nuova, UO di Oncologia Medica
  • Roma, Italy, 00151
    • Recruiting
    • Azienda Ospedaliera S. Camillo-Forlanini, U.O. di Oncologia Medica
  • Sassari, Italy, 07100
    • Recruiting
    • Ospedale SS. Annunziata, UO di Oncologia Medica
  • Torino, Italy, 10126
    • Recruiting
    • Azienda Sanitaria Ospedaliera Molinette, U.O. di Oncologia Medica
  • Treviglio, BG, Italy, 24047
    • Not yet recruiting
    • P.O. Treviglio-Caravaggio, U.O. di Oncologia Medica
    • Principal Investigator: Barni Sandro, MD
  • Verona, Italy, 37126
    • Recruiting
    • Policlinico "G. B. Rossi"-Borgo Roma, U.O. di Oncologia Medica Clinicizzata
    • Principal Investigator: Antonio Santo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A; Monochemotherapy	Drug: Pemetrexed; Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 of a 21 days cycle
EXPERIMENTAL: B; Combination chemotherapy	Drug: Pemetrexed plus carboplatin; Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 and Carboplatin AUC 5 i.v. over approximately 30 minutes on day 1 (beginning approximately 30 minutes after the end of the pemetrexed infusion) of a 21 days cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess differences in terms of response rate between the combination pemetrexed-carboplatin and pemetrexed alone.	3 months
To assess differences in terms of duration of response between the combination pemetrexed-carboplatin and pemetrexed alone.	36 months
To assess differences in terms of toxicity between the combination pemetrexed-carboplatin and pemetrexed alone.	3 months
To assess differences in terms of survival between the combination pemetrexed-carboplatin and pemetrexed alone.	36 months

Collaborators and Investigators

• Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
• Investigators: Principal Investigator: Andrea Ardizzoni, MD, Gruppo Oncologico Italiano di Ricerca Clinica

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ANTICIPATED): July 1, 2009
• Study Completion (ANTICIPATED): December 1, 2009

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: November 5, 2008
• First Posted (ESTIMATE): November 6, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 3, 2009
• Last Update Submitted That Met QC Criteria: July 31, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: carboplatin; pemetrexed; second line treatment
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: GOIRC 02/2006; EudraCT number 2006-004009-24