Clinical trial NCT00744900: Pemetrexed Plus Cisplatin for Brain Metastasis of Advanced Non - Small Cell Lung Cancer (NSCLC)
Official title: A Phase II Trial With Pemetrexed Plus Cisplatin as First Line Chemotherapy for Advanced Non - Small Cell Lung Cancer (NSCLC) Patients With Measurable Asymptomatic Brain Metastasis (GFPC 07-01/METAL).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Pemetrexed, Non-Small Cell Lung Cancer, brain metastasis
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2008-09-01
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).
* Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
* Peripheral neuropathy \> CTC Grade 2
* Patient compliance or geographic distance precluding adequate follow up.

Primary outcomes:
measure: Objective of this study is overall response rate on brain metastasis according to RECIST criteria.
timeFrame: After cycles 2, 4 and 6 and every 6 weeks after study drug completion in absence of disease progression.
Secondary outcomes:
measure: Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms and overall survival.
timeFrame: After cycles 2, 4 and 6 and every 6 weeks after study drug completion.
Other outcomes:
Locations:
city: Aix En Provence
country: France
facility: Centre Hôspitalier du Pays d'Aix, Service des Maladies Respiratoires
city: Angers
country: France
facility: CHU d'Angers, Service de Pneumologie
city: Antibes
country: France
facility: Médecine 4, C.H.G. de la Fontonne Antibes
city: Brest
country: France
facility: CHU brest, institut de cancérologie et d'hématologie
city: Caen
country: France
facility: Centre François Baclesse
city: Cergy Pontoise
country: France
facility: Centre Hospitalier René Dubos - Pontoise, Service d'Oncologie - Hématologie Clinique
city: Charleville
country: France
facility: Centre Hospitalier, Service de Pneumologie
city: Creteil
country: France
facility: CHI, Service de Pneumologie
city: Draguignan
country: France
facility: Pneumologie, Centre hôspitalier, DRAGUIGNAN
city: GAP
country: France
facility: CH GAP
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental, Service de Pneumologie,
city: Le Chesnay
country: France
facility: Hôpital A. Mignot, Service de Pneumologie
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Mantes La Jolie
country: France
facility: Centre Hôspitalier, Service de Pneumo-Neuro
city: Marseilles
country: France
facility: Hôpital Sainte Margueritte
city: Martigues
country: France
facility: Serv. de Pneumo-Allergo, CH de Martigues
city: Paris
country: France
facility: Serv. de Pneumo - Hôpital St Antoine
city: Pierre-benite
country: France
facility: Service Pneumologie, Pavillon 1A, CH de Lyon-Sud
city: Rennes
country: France
facility: Hôpital Pontchailloux, Service de Pneumologie.
city: Roanne
country: France
facility: CHG, Service de Pneumologie
city: Rouen
country: France
facility: Luc THIBERVILLE
city: Rouen
country: France
facility: CHU de ROUEN, Hôpital Bois Guillaume, Serv. de Pneumo.
city: Saint-Priest en Jarez Cedex
country: France
facility: Institut de Cancérologie de la Loire
city: Toulouse
country: France
facility: CHU, Service du Pr. Carles
city: VILLEFRANCHE sur SAONE
country: France
facility: Pneumologie, Centre Hospitalier
Study officials:
affiliation: CHU Brest
name: Gilles Robinet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique Hôpitaux de Marseille
name: Barlesi Barlesi, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier, Créteil
name: Isabelle Monet, MD
role: PRINCIPAL_INVESTIGATOR
References: