Pemetrexed Plus Cisplatin for Brain Metastasis of Advanced Non - Small Cell Lung Cancer (NSCLC)

NCT00744900 | Completed Phase 2 DMC

• 2 other identifiers: GFPC 07-01RB 07.103
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 25

Brief Summary

NSCLC patients often have cerebral metastasis : 10% at diagnosis and 40% during disease management. Neurosurgery is not indicated in the majority of cases because of presence of several lesions in the brain, failure of primary tumor control or presence of extra-cerebral metastasis. Cerebral metastasis lead to death in 30 to 50% of these cases. Management of these patients in this situation is based on supportive care and whole-brain radiotherapy. The place of chemotherapy for patients with good performance status was discussed for a long time and it is now admitted. However, the place of new drugs such as pemetrexed, which is currently used as a second line treatment for NSCLC, needs to be further studied. It is known that pemetrexed when added to cisplatin for treatment of NSCLC provides a similar effectiveness when compared to other drugs associations commonly used in this indication. In addition, Cisplatin with Pemetrexed probably present a better safety profile. The present study is based upon the hypothesis stipulating that the association cisplatin-pemetrexed will be at least as efficient as the others association currently used for treatment of NSCLC and will present a better safety profile. The primary objective of this study is overall response rate on brain metastasis according to RECIST criteria. Secondary judgment criterias are : Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms, overall survival. The trial will enroll up to 45 patients in this single-arm two-stage sequential phase II study with the possibility of stopping the study early because of lack of efficacy.

Conditions

Lung Cancer

Keywords

Pemetrexed, Non-Small Cell Lung Cancer, brain metastasis

Outcome Measures

Primary Outcomes (1)

• Objective of this study is overall response rate on brain metastasis according to RECIST criteria.

  After cycles 2, 4 and 6 and every 6 weeks after study drug completion in absence of disease progression.

Secondary Outcomes (1)

• Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms and overall survival.

  After cycles 2, 4 and 6 and every 6 weeks after study drug completion.

Study Arms (1)

A

EXPERIMENTAL

Drug: Pemetrexed, cisplatin

Interventions

Pemetrexed, cisplatin DRUG

Alimta 500mg/m² IV 10 min infusion and Cisplatin 75mg/m² IV 60 min on day 1. Cycle will be repeated each 21 days.Folic acid orally 400µg should begin 5-7days prior to the first dose of pemetrexed and continuing daily until 3 weeks after the last dose of pemetrexed. Vitamin B12 will be administered as a 1000 mg intramuscular injection, approximately one week before Day 1 of cycle 1 and should repeat approximately every 9 weeks Dexamethasone, 4 mg or equivalent, should be taken orally twice per day on the day before, the day of, and the day after each dose of pemetrexed.WBRT will be administered with high energy photons systematically after cycle 6 or in case of stable disease (SD) after cycle 4 or progressive disease (PD) at any time. The dose will be 3Gy by fraction, 1 fraction per day, for 10 days.

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with cytologically or histologically confirmed NSCLC.
• Patient with brain metastasis not amenable to surgery or radiosurgery with curative intent
• At least one brain measurable lesion using RECIST criteria
• ECOG Performance Status ≤2
• No prior chemotherapy for this cancer
• Prior surgery is allowed provided there is a relapse or progression after the procedure.
• Adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) superior or equal to 1.5 X109/L, platelets superior or equal to 100 X 109/L, and hemoglobin superior or equal to 9 g/dL; Hepatic: bilirubin \<1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) \<3xULN (or \<5xULN with liver metastases); Renal: Calculated creatinine clearance (CrCl) superior or equal to 45mL/min based on the standard Cockroft and Gault formula
• Signed informed consent document from the patient
• Patient must be at least 18 years of age.
• Estimated life expectancy of at least 12 weeks.
• Effective contraception (men and women) for and during the 6 months following the end of treatment

You may not qualify if:

• Symptomatic brain metastasis
• Have received prior radiotherapy for brain metastasis
• Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures.
• A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade \[Gleason score \<6\] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
• Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete study.
• Inability to discontinue administration of aspirin at a dose \>1.3g/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).
• Peripheral neuropathy \> CTC Grade 2
• Patient compliance or geographic distance precluding adequate follow up.

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (25)

Centre Hôspitalier du Pays d'Aix, Service des Maladies Respiratoires

Aix-en-Provence, 13616, France

Location

CHU d'Angers, Service de Pneumologie

Angers, 49033, France

Location

Médecine 4, C.H.G. de la Fontonne Antibes

Antibes, 06606, France

Location

CHU brest, institut de cancérologie et d'hématologie

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Hospitalier René Dubos - Pontoise, Service d'Oncologie - Hématologie Clinique

Cergy-Pontoise, 95303, France

Location

Centre Hospitalier, Service de Pneumologie

Charleville, 08 000, France

Location

CHI, Service de Pneumologie

Créteil, 94010, France

Location

Pneumologie, Centre hôspitalier, DRAGUIGNAN

Draguignan, 83300, France

Location

CH GAP

Gap, 05000, France

Location

Centre Hospitalier Départemental, Service de Pneumologie,

La Roche-sur-Yon, 85000, France

Location

Hôpital A. Mignot, Service de Pneumologie

Le Chesnay, 78157, France

Location

Hopital de la Croix Rousse

Lyon, 69317, France

Location

Centre Hôspitalier, Service de Pneumo-Neuro

Mantes-la-Jolie, 78200, France

Location

Hôpital Sainte Margueritte

Marseille, 13274, France

Location

Serv. de Pneumo-Allergo, CH de Martigues

Martigues, 13695, France

Location

Serv. de Pneumo - Hôpital St Antoine

Paris, 75571, France

Location

Service Pneumologie, Pavillon 1A, CH de Lyon-Sud

Pierre-Bénite, 69495, France

Location

Hôpital Pontchailloux, Service de Pneumologie.

Rennes, 35033, France

Location

CHG, Service de Pneumologie

Roanne, 42300, France

Location

Luc THIBERVILLE

Rouen, 76031, France

Location

CHU de ROUEN, Hôpital Bois Guillaume, Serv. de Pneumo.

Rouen, 76233, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, 42271, France

Location

CHU, Service du Pr. Carles

Toulouse, 31059, France

Location

Pneumologie, Centre Hospitalier

Villefranche-sur-Saône, 69655, France

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gilles Robinet, MD

  CHU Brest

  PRINCIPAL INVESTIGATOR

• Barlesi Barlesi, MD, Ph.D

  Assistance Publique Hôpitaux de Marseille

  PRINCIPAL INVESTIGATOR

• Isabelle Monet, MD

  Centre Hospitalier, Créteil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 29, 2008
• First Posted: September 1, 2008
• Study Start: September 1, 2008
• Last Updated: July 28, 2009

Record last verified: 2009-07

Locations

FR (25)