Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours (CLARINET)

• ClinicalTrials.gov Identifier: NCT00353496
• Recruitment Status: Completed
• First Posted: July 18, 2006
• Results First Posted: February 18, 2015
• Last Update Posted: October 12, 2022
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: July 17, 2006
• First Posted Date: July 18, 2006
• Results First Submitted Date: January 15, 2015
• Results First Posted Date: February 18, 2015
• Last Update Posted Date: October 12, 2022
• Study Start Date: June 2006
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2015)

Progression-Free Survival (PFS) [ Time Frame: From randomisation up to the last tumour assessment (scheduled at 96 weeks). Radiological scans were performed every 12 weeks during the first year and every 24 weeks during the second year ]

Time from randomization to first documentation of disease progression, or death. Disease progression centrally assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.0

• Original Primary Outcome Measures (submitted: July 17, 2006): Time to either disease progression or death within 96 weeks after the first study drug administration.

Current Secondary Outcome Measures (submitted: February 17, 2015)

• Percentage of Patients Alive & Without Disease Progression [ Time Frame: Week 48 & 96 ]
  Percentage of patients still ongoing (or completing at Week 96) without centrally assessed disease progression or death at Weeks 48 and 96.
• Pharmacokinetic Profile of Lanreotide [ Time Frame: Week 4, 12, 24, 36, 48, 72, 96 ]
  Pharmacokinetic Profile of Lanreotide assessed by mean serum concentration at specified timepoints
• Change in the Global Health Status Quality of Life Assessment [ Time Frame: Week 12 to Week 96 (last visit) ]
  Transformed scores from European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire responses (QLQ)-C30. Questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.
• Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels [ Time Frame: Week 12 to Week 96 (last visit) ]
• Percentage of Patients Still Alive Based on Available Overall Survival Data [ Time Frame: Randomisation to death or last visit, up to 321 weeks ]
  Overall survival defined as the time from randomisation to death due to any cause. Subjects were followed for overall survival beyond study completion/withdrawal via annual telephone contact until the last subject completed the study.

Original Secondary Outcome Measures (submitted: July 17, 2006)

• To compare the effect of lanreotide Autogel and placebo on the time to progression, quality of life and on tumour markers
• Side effects of the treatment will be assessed
• Pharmacokinetic profile of lanreotide will be assessed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours
• Official Title: Phase III, Randomised, Double-blind, Stratified Comparative, Placebo Controlled, Parallel Group, Multi-centre Study to Assess the Effect of Deep Subcutaneous Injections of Lanreotide Autogel 120mg Administered Every 28 Days on Tumour Progression Free Survival in Patients With Non-functioning Entero-pancreatic Endocrine Tumour
• Brief Summary: The study will compare the difference between lanreotide Autogel and placebo on progression free survival in patients who have an endocrine tumour in the pancreas or intestines.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Endocrine Tumors

Intervention

• Drug: lanreotide (Autogel formulation)
  120mg administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.
• Drug: Placebo
  Saline solution 0.9% administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.

Study Arms

• Experimental: lanreotide (Autogel formulation)
  Intervention: Drug: lanreotide (Autogel formulation)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Publications *

• Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlackova E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. doi: 10.1056/NEJMoa1316158.
• Caplin ME, Pavel M, Phan AT, Cwikla JB, Sedlackova E, Thanh XT, Wolin EM, Ruszniewski P; CLARINET Investigators. Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study. Endocrine. 2021 Feb;71(2):502-513. doi: 10.1007/s12020-020-02475-2. Epub 2020 Oct 14.
• Lybaert W, Van Hul E, Woestenborghs H. Long-term disease control of a pancreatic neuroendocrine tumor with lanreotide autogel((R)): a case report. Case Rep Oncol. 2014 Sep 26;7(3):673-80. doi: 10.1159/000368207. eCollection 2014 Sep.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 29, 2013): 264
• Original Enrollment (submitted: July 17, 2006): 200
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Endocrine tumour in the intestine or pancreas and with locally advanced or metastatic disease
• No hormone related symptoms
• Well or moderately differentiated tumour confirmed by histology
• Tumour lesions which are measurable by a CT or MRI scan

Exclusion Criteria:

• Previously treated with a somatostatin analogue unless more than 6 months ago and given for no more than 15 days
• Treated within the last 6 months with interferon, chemoembolisation or chemotherapy or at any time with a radionuclide
• Had a previous cancer except basal cell carcinoma and/or in situ carcinoma of the cervix/uterus and/or patients treated with curative intent and free from disease for 5 years
• Pregnant or lactating
• Females must use adequate contraception during the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Czechia, Denmark, France, Germany, India, Italy, Netherlands, Poland, Slovakia, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00353496
• Other Study ID Numbers: 2-55-52030-726; 2005-004904-35 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Not Provided
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director, Endocrinology; Ipsen

• PRS Account: Ipsen
• Verification Date: September 2022