Treatment of Unresecable and/or Metastatic Merkel Cell Carcinoma by Somatostatine Analogues (PHRC-Merkel)
Primary Purpose
Carcinoma, Merkel Cell
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Lanreotide
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Merkel Cell focused on measuring lanreotide
Eligibility Criteria
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
- 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
Sites / Locations
- Grenoble University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Only one arm
Arm Description
All patients receive Lanreotide.
Outcomes
Primary Outcome Measures
Percentage of patient with positive response according to the RECIST 1.1 criteria
Positive response will be defined according to the RECIST 1.1 criteria
Secondary Outcome Measures
Percentage of patient with positive response according to the RECIST 1.1 criteria
Positive response will be defined according to the RECIST 1.1
Number of Participants with Adverse Events
Description of the safety and tolerability of lanreotide in this study
Full Information
NCT ID
NCT02351128
First Posted
January 13, 2015
Last Updated
October 17, 2017
Sponsor
University Hospital, Grenoble
1. Study Identification
Unique Protocol Identification Number
NCT02351128
Brief Title
Treatment of Unresecable and/or Metastatic Merkel Cell Carcinoma by Somatostatine Analogues
Acronym
PHRC-Merkel
Official Title
Traitement Des Carcinomes à Cellules de Merkel inopérables et/ou métastatiques Par Analogue de la Somatostatine - Etude Nationale Multicentrique Mono-bras de Phase II.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
May 15, 2017 (Actual)
Study Completion Date
May 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the efficacy of lanreotide on locally evolving and/or metastatic MCC in a national prospective multicentre phase II study (centres belonging to the skin cancer task force of the French Society of Dermatology namely "Groupe de Cancérologie Cutanée de la Société Française de Dermatologie"). This one-arm study, for which the primary endpoint is overall response to lanreotide, will follow an A'Hern plan in one step (A'Hern RP. Sample size tables for exact single-stage phase II designs. Stat Med 2001, 20:859-66) with main evaluation at 12 weeks on a population of 35 patients. The investigators make assumption that a 40% success rate at 3 months would be desirable, but if it was 20% or less the treatment would be unacceptable. It gives a trial size of 35 patients with a cut-off of 12 patients. Over 12 patients lanreotide will be considered as effective.
The lanreotide treatment (Somatuline LP 120 mg injected subcutaneously every 28 days) will be provided by IPSEN Pharma laboratory. An ancillary immunohistochemistry study on somatostatine receptors 2,3,5, dopamine receptors 1,2 and polyomavirus MCPyV will bring new data on this neuroendocrine tumour and potentially provide new therapeutic perspectives.
The results of this study may :
determine whether somatostatin analogues may help to treat locally advanced and/or metastatic MCC;
address whether there is a correlation between positive SPECT-CT (octreoscan) assessment and therapeutic response to lanreotide;
evaluate the place of TEP-CT and SPECT-CT for MCC evaluation/staging;
evaluate in future studies, with the ancillary data, other analogues or hybrid molecules;
consider, if positive results are obtained from this study, somatostatin analogues as adjuvant treatment after surgery of primary MCC.
Detailed Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Merkel Cell
Keywords
lanreotide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Only one arm
Arm Type
Experimental
Arm Description
All patients receive Lanreotide.
Intervention Type
Drug
Intervention Name(s)
Lanreotide
Other Intervention Name(s)
Somatuline
Primary Outcome Measure Information:
Title
Percentage of patient with positive response according to the RECIST 1.1 criteria
Description
Positive response will be defined according to the RECIST 1.1 criteria
Time Frame
at 3 months
Secondary Outcome Measure Information:
Title
Percentage of patient with positive response according to the RECIST 1.1 criteria
Description
Positive response will be defined according to the RECIST 1.1
Time Frame
at 6, 9,12,18 and 24 months
Title
Number of Participants with Adverse Events
Description
Description of the safety and tolerability of lanreotide in this study
Time Frame
at 3,6, 9,12,18 and 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BEYLOT-BARY Marie
Organizational Affiliation
Bordeaux University Hospital, Haut-lévêque
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DUTRIAUX Carole
Organizational Affiliation
Bordeaux University Hospital, St André
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DALAC Sophie
Organizational Affiliation
Centre Hospitalier Universitaire Dijon
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DUPUY Alain
Organizational Affiliation
Rennes University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
LEBBE Céleste
Organizational Affiliation
AP-HP- Saint Louis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
AVRIL Marie-Françoise
Organizational Affiliation
AP-HP - Cochin
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DALLE Stéphane
Organizational Affiliation
HCL- Lyon Sud, Pierre Bénite
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GUILLOT Bernard
Organizational Affiliation
Montpellier University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
VERNEUIL Laurence
Organizational Affiliation
University Hospital, Caen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DRENO Brigitte
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
HAINAUT-Wierzbicka Ewa
Organizational Affiliation
Poitiers University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GROB Jean-Jacques
Organizational Affiliation
AP-HM
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DEQUATREBARBES Julie
Organizational Affiliation
Annecy Interregional Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
ZEHOU Ouidad
Organizational Affiliation
AP-HP-Henri MONDOR
Official's Role
Principal Investigator
Facility Information:
Facility Name
Grenoble University Hospital
City
Grenoble
ZIP/Postal Code
38 000
Country
France
12. IPD Sharing Statement
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Treatment of Unresecable and/or Metastatic Merkel Cell Carcinoma by Somatostatine Analogues
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