E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive advanced/metastatic midgut carcinoid tumors |
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E.1.1.1 | Medical condition in easily understood language |
Progressive advanced/metastatic intestinal endocrine tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068118 |
E.1.2 | Term | Metastatic carcinoid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of the combination of sunitinib with lanreotide and of placebo with lanreotide regarding progression-free-survival (PFS) as assessed by local investigators |
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E.2.2 | Secondary objectives of the trial |
To evaluate overall survival (OS) in sunitinib- and placebo-treated subjects. - To evaluate duration of response (DR) in sunitinib- and placebo-treated subjects in subjects achieving a response. - To evaluate objective response (OR) rate in sunitinib- and placebo-treated subjects. - To assess time to tumor response (TTR) for sunitinib- and placebo-treated subjects. - To assess Health related Quality of life (EORTC QLQ C-30). - To evaluate the symptomatic effects of sunitinib in subject with carcinoid syndrom. - To evaluate the best biological responses as assessed using serum chromogranin A and urine 5HIAA for sunitinib- and placebo-treated subjects. - To evaluate plasma levels of VEGF-A, VEGF-C, sKIT, and sVEGFR2 as determined by Elisa assay for sunitinib- and placebo-treated subjects, at baseline, 1-month treatment, at first tumor evaluation and at the end of study treatment (optional). - To assess safety and tolerability of sunitinib in the study population
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Patients with midgut well-differentiated Grade 1-2 endocrine tumor (ENETS guidelines). Pathological confirmation might have been obtained from primary tumor (surgical resection), or lymph node/liver metastases. Histologically documented endocrine liver metastases with unknown primary are eligible if the patient has history of carcinoid syndrome with elevated serum chromogranin A and urinary 5HIAA levels. * Local, locally advanced or metastatic disease documented as progressive by RECIST v1.1. on CT-scan or MRI at baseline and within 12 months prior to baseline. The previous scans will be used to classify the patient as having progressive disease at baseline according to RECIST v1.1 criteria. Octreoscan results may be used to document progressive disease at baseline, but not for RECIST v1.1 determination during the study. Locally advanced liver metastasis, corresponding to >50% liver involvement as documented on baseline CT-scan or MRI by the local investigator, are eligible regardless prior progression * 5HIAA levels >=1.5ULN as measured in each individual centre * Disease that is not amenable to surgery with curative intent * ECOG Performance status 0 or 1 * Age more than 18 years * Able to swallow oral compound |
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E.4 | Principal exclusion criteria |
* Patients with undifferentiated, poorly differentiated gastrointestinal neuroendocrine tumors, pancreatic neuroendocrine tumors, bronchial carcinoid tumors (WHO 2010 classification) * Patients with carcinoid tumors with the presence of an obstructive intestinal tumor * Patients with uncontrolled cardiac complication as part of their carcinoid syndrome * Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational anticancer agent *Current treatment with dose ≥ 120 mg per month of lanreotide * Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors (such as bevacizumab, sorafenib, or sunitinib). Prior treatment with non-VEGF-targeted angiogenic inhibitors such as everolimus or temsirolimus is permitted * Patients who stopped everolimus treatment was less than 4 weeks prior to randomization * Patients with concomitant treatment with interferon * Concomitant treatment with a drug having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide) * Unstable systemic diseases including uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy) or active uncontrolled infections * Patients with complicated, untreated lithiasis of the bile ducts * Ongoing cardiac dysrhythmias of NCI CTC grade 2, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free-Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD |
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E.5.2 | Secondary end point(s) |
- Overall survival is defined as the time from date of randomization to date of death. In the absence of confirmation of death, survival time will be censored to last date the subject is known to be alive. - The objective response (OR) is the overall objective response recorded from randomization until disease progression: sustained complete response (CR) or partial response (PR) according to RECIST v1.1 definitions for at least 4 weeks, confirmed by tumor assessments. - Duration of response (DR) is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival :time from date of randomization to date of death. In the absence of confirmation of death, survival time will be censored to last date the subject is known to be alive. Overall objective response: recorded from randomization until disease progression Duration of response:time from the first documentation of objective tumor response |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | Yes |
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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Last visit of the last subject |
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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 |