Clinical Drug Experience Knowledgebase

Traitement Des Carcinomes à Cellules de Merkel inopérables et/ou métastatiques Par Analogue de la Somatostatine - Etude Nationale Multicentrique Mono-bras de Phase II.

The efficacy will be considered as success if patient have a positive response to lanreotide.

Primary criterion Positive response at 3 months will be defined according to the RECIST 1.1 criteria (clinical and TDM evaluation will be done at 3 months): complete response (CR) or partial response (PR) or stable disease (SD) at 3 months.

Secondary Objectives:

Assessment of the primary criterion at M6, M9, M12, M18 and M24
Description of the overall survival and time to progression
Assessment of the efficacy of the following radiological exams for staging the disease: SPECT-CT and TEP-CT
Description of the correlation of SPECT-CT results (positivity or negativity) and response to treatment, and the correlation of TEP-CT results and response to treatment
Description of the safety and tolerability of lanreotide in this study

Population and Methods

Experimental plan French national prospective multicentre phase II one-arm study. This one-arm study, for which the primary endpoint is overall response to lanreotide, will follow an A'Hern plan in one step.

Population Inclusion criteria

Histologically confirmed neuroendocrine carcinoma of the skin (Merkel cell carcinoma) with inoperable local-regional disease or distant metastatic disease (stages IIIB or IV AJCC 2010), cerebral nervous system metastases will be allowed.
First line of treatment or more
Measurable disease: at least 20 mm by conventional techniques or 10 mm by spiral CT scan
Age 18 years or older;
WHO performance status ECOG 0-3
premenopausal patients must use effective contraception
No other prior malignancy within 5 years except adequately treated basal cell or squamous cell carcinoma or in situ cancer of the cervix
No other concurrent chemotherapy, immunotherapy or hormone therapy.
At least 4 weeks since adjuvant chemotherapy, 14 days since radiotherapy and 2 weeks since surgery
Biological functions: absolute neutrophil count at least 1000/mm3, platelet count at least 100000/mm3, haemoglobin at least 9g/dl (transfusion allowed), bilirubin no greater than 3 times upper limit of normal (ULN), SGOT and SGPT no greater than 2.5 times ULN, no untreated chronic liver disease, creatinine no greater than 1.5 times ULN, no untreated chronic renal disease, no untreated diabetes or infection
Written informed consent

Exclusion criteria

previous hypersensibility to lanreotide treatment
complicated and untreated cholelithiasis
pregnancy or breast-feeding
patient treated with cyclosporine

Studied treatment Lanreotide 120 mg sub-cutaneously every 28 days during 12 weeks, followed by injections every 28 days if response is positive until progression. The expected rate of positive response is 50% of patients at 3 months and 25% of patients at 1 year.

Evaluation Criteria and follow-up of the study The inclusions will be done during 2 years and the follow-up of patients is planned to be 2 years, to have an optimal assessment of progression free survival in case of response to treatment, with a total study duration of 4 years.

Data collection

at inclusion : patient's demography and medical history; clinical and anatomopathological data on primary MCC; blood count, platelets, electrolytes, glucose, creatinine, transaminases, bilirubin, ECG, pregnancy test for women of childbearing age;
Clinical examination and measure of possible target lesions (tumor and cutaneous metastasis) using RECIST 1.1 criteria at inclusion and at M1, M2 and M3 and every 3 months during the first year (M6, M9 and M12) and every 6 months during the second year of follow-up (M18 and M24);
Cerebral and thoraco-abdominal CTscan with results of imaging (RECIST 1.1 criteria: http://www.recist.com/recist-in-practice/01.html) at inclusion, at 3 months and, every 3 months during the first year, every 6 months during 2nd year;
Octreoscan (SPECT-CT) at inclusion
PET-CT at inclusion