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Pemetrexed Plus Cisplatin for Brain Metastasis of Advanced Non - Small Cell Lung Cancer (NSCLC) (GFPC 07-01)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Brest
ClinicalTrials.gov Identifier:
NCT00744900
First received: August 29, 2008
Last updated: July 24, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: Pemetrexed, cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by University Hospital, Brest:

Primary Outcome Measures:
  • Objective of this study is overall response rate on brain metastasis according to RECIST criteria. [ Time Frame: After cycles 2, 4 and 6 and every 6 weeks after study drug completion in absence of disease progression. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms and overall survival. [ Time Frame: After cycles 2, 4 and 6 and every 6 weeks after study drug completion. ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: September 2008
Arms Assigned Interventions
Experimental: A Drug: Pemetrexed, cisplatin
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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 ClinicalTrials.gov identifier: NCT00744900

Locations
France
Centre Hôspitalier du Pays d'Aix, Service des Maladies Respiratoires
Aix En Provence, France, 13616
CHU d'Angers, Service de Pneumologie
Angers, France, 49033
Médecine 4, C.H.G. de la Fontonne Antibes
Antibes, France, 06606
CHU brest, institut de cancérologie et d'hématologie
Brest, France, 29200
Centre François Baclesse
Caen, France, 14000
Centre Hospitalier René Dubos - Pontoise, Service d'Oncologie - Hématologie Clinique
Cergy Pontoise, France, 95303
Centre Hospitalier, Service de Pneumologie
Charleville, France, 08 000
CHI, Service de Pneumologie
Creteil, France, 94010
Pneumologie, Centre hôspitalier, DRAGUIGNAN
Draguignan, France, 83300
CH GAP
GAP, France, 05000
Centre Hospitalier Départemental, Service de Pneumologie,
La Roche Sur Yon, France, 85000
Hôpital A. Mignot, Service de Pneumologie
Le Chesnay, France, 78157
Hopital de la Croix Rousse
Lyon, France, 69317
Centre Hôspitalier, Service de Pneumo-Neuro
Mantes La Jolie, France, 78200
Hôpital Sainte Margueritte
Marseilles, France, 13274
Serv. de Pneumo-Allergo, CH de Martigues
Martigues, France, 13695
Serv. de Pneumo - Hôpital St Antoine
Paris, France, 75571
Service Pneumologie, Pavillon 1A, CH de Lyon-Sud
Pierre-benite, France, 69495
Hôpital Pontchailloux, Service de Pneumologie.
Rennes, France, 35033
CHG, Service de Pneumologie
Roanne, France, 42300
CHU de ROUEN, Hôpital Bois Guillaume, Serv. de Pneumo.
Rouen, France, 76233
Luc THIBERVILLE
Rouen, France, 76031
Institut de Cancérologie de la Loire
Saint-Priest en Jarez Cedex, France, 42271
CHU, Service du Pr. Carles
Toulouse, France, 31059
Pneumologie, Centre Hospitalier
VILLEFRANCHE sur SAONE, France, 69655
Sponsors and Collaborators
University Hospital, Brest
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Gilles ROBINET/MD, CHU BREST, Institut de Cancerologie et d'Hématologie
ClinicalTrials.gov Identifier: NCT00744900     History of Changes
Other Study ID Numbers: GFPC 07-01, RB 07.103
Study First Received: August 29, 2008
Last Updated: July 24, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Brest:
Pemetrexed, Non-Small Cell Lung Cancer, brain metastasis

Additional relevant MeSH terms:
Lung Neoplasms
Neoplasm Metastasis
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014