E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
well differentiated, metastatic or locally advanced, unresectable pancreatic or midgut neuroendocrine tumours |
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E.1.1.1 | Medical condition in easily understood language |
pancreatic or midgut neuroendocrine tumours |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052399 |
E.1.2 | Term | Neuroendocrine tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess progression free survival (PFS) when treated with lanreotide Autogel® 120 mg administered every 14 days based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.0, and according to central review |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the clinical and biological safety profile.
•To evaluate time to progression.
•To evaluate PFS rate every 12 weeks.
•To evaluate overall survival at Week 48 and at the end of the study period in each cohort.
•To evaluate the objective response rate (ORR) as per RECIST v1.0 every 12 weeks.
•To evaluate the disease control rate (DCR) as per RECIST v1.0 at Weeks 24 and 48 and at the end of study period in each cohort.
•To evaluate the best overall response as per RECIST v1.0.
•To evaluate the duration of stable disease (SD) as per RECIST v1.0.
•To detect predictive factors of PFS.
•To evaluate the effect on symptoms (diarrhoea, flushing).
•To evaluate quality of life.
•To evaluate the changes in nonspecific (Chromogranin A (CgA), neuron specific enolase (NSE) and 5 hydroxyindoleacetic acid (5 HIAA) and specific peptide tumour biomarkers.
•To evaluate the appearance of antilanreotide antibodies.
•To evaluate the pharmacokinetic (PK) profile of lanreotide |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female subjects aged 18 years old or older.
2) Histopathologically confirmed well differentiated (grade 1 or grade 2 according to the WHO 2010 classification), metastatic or locally advanced, unresectable pNET (pNET cohort) or midgut NET (midgut cohort) with or without hormone related syndromes, with a proliferation index (Ki67) ≤20%.
3) Positive somatostatin receptors type 2 (SSTR2) as assessed by imaging (scintigraphy or positron emission tomography (PET) scan) in the organs of target lesions.
4) Progression as assessed by an independent central reviewer according to RECIST v1.0 from radiological imaging (CT scan or MRI) while receiving first line treatment with lanreotide Autogel® at a standard dose of 120 mg every 28 days for at least 24 weeks (6 injections). Progression must be radiologically documented using the same technique of images (CT scan or MRI) within 24 months prior to enrolment. Inclusion into the study must be within 28 days of the radiological imaging that is performed to document progression.
5) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
6) Provision of written informed consent prior to any study related procedures.
7) Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must provide a negative urine pregnancy test at Screening, and use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 2 months after participation in the study. Acceptable methods of contraception include double barrier method, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted and injected).
8) Subjects must be willing and able to comply with study restrictions and willing to return to the clinic for the follow up evaluation as specified in the protocol.
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|
E.4 | Principal exclusion criteria |
1) Has poorly differentiated grade 3 NET or rapidly progressive NET (within 12 weeks of initiation of lanreotide Autogel® 120 mg every 28 days) as per RECIST v1.0.
2) Has been diagnosed with VIPoma (i.e. Verner Morrison syndrome), insulinoma, foregut (except for pNET), hindgut NET, unknown primary NET or multiple endocrine neoplasms (MEN).
3) Has progressed during treatment with somatostatin analogues (SSAs) other than lanreotide Autogel® 120 mg.
4) Has been previously treated with any antitumour agent for NET other than lanreotide Autogel® 120 mg every 28 days: chemotherapy, molecular targeted therapy, peptide receptor radionuclide therapy (PRRT) or interferon. Exception made of prior treatment with Octreotide at standard dose stopped for other reason than disease progression.
5) Has had major surgery related to the studied disease within 3 months prior to entering the study. Previous debulking surgery and liver-directed therapies are acceptable as long as tumour burden is measurable (other target lesions).
6) Has symptomatic gallbladder lithiasis/sludge at Screening or a history of symptomatic cholelithiasis with no cholecystectomy since then.
7) Has had previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of the cervix/uterus if subjects treated with curative intent and free from disease for more than 5 years).
8) Was treated with any other investigational medicinal product (IMP) within the last 30 days before study entry.
9) Is pregnant or lactating.
10) Has abnormal findings at Screening, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety.
11) Has any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
12) Has been previously screened in this study, exception made of subjects who screen-failed following central reviewers eligibility
assessment (ie non PD).
13) Has a history of hypersensitivity to lanreotide Autogel® or drugs with a similar chemical structure, or any excipient used in the formulation.
14) Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
15) Has a history of, or known current, problems with substance or alcohol abuse.
16) Vulnerable subjects (i.e. subjects who are under legal protection,
who are interned due to a mental disease and who are kept in
detention).
17) Subjects who have a link with the sponsor, the clinical trial site or
the investigator (medical, pharmacy, dental and nursing students,
subordinate hospital and laboratory personnel, employees of the
sponsor). |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• every 12 weeks or death date
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E.5.2 | Secondary end point(s) |
• Median time to progression
• Proportion of subjects alive and without progression
• Overall survival
• ORR
• DCR
• Best overall response
• Median duration of SD
• Factors associated with PFS
• Symptom control (diarrhoea and flushing)
• Quality of life
• pNET cohort: nonspecific and pNET specific tumour biomarker concentrations
• Midgut cohort: nonspecific tumour biomarker concentrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Defined time points of evaluation for each end point as per protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |