E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diagnosis of malignant PPGL, based on imaging or biopsy evidence of metastases in liver, bones, lungs and or lymph nodes, combined with at least one of two further confirmatory diagnoses: 1. diagnosis of PPGL from histopathological review of resected or biopsied tissue performed by a skilled pathologist or 2. in patients where tumor tissue is unavailable for formal pathological review, from combined biochemical and functional imaging evidence of PPGL |
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E.1.1.1 | Medical condition in easily understood language |
MALIGNANT PROGRESSIVE PHEOCHROMOCYTOMA AND PARAGANGLIOMA (PPGL) |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033792 |
E.1.2 | Term | Paraganglion neoplasm NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 determine the efficacy of Sunitinib on the progression-free survival at 12 months in subjects with progressive malignant pheochromocytoma and paraganglioma treated with sunitinib at a starting dose of 37.5 mg daily (continuous dosing). |
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E.2.2 | Secondary objectives of the trial |
-To determine overall survival and progression free survival. -To determine time to progression. -To determine objective response rate at one year. -To determine time to and duration of tumor response. -To assess safety profile including a dedicated cardiovascular management.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Diagnosis of malignant PPGL, -Metastatic disease not amenable to surgical resection -Pre-treated or not -Whatever the genetic status (sporadic or inherited) -Evaluable disease according to RECIST 1.1 criteria -ECOG performance status 0-2 -Life expectancy ≥ 6 months as prognosticated by the physician -Age ≥ 18 years, no superior limit -Adequate bone marrow reserve (Hb > 8, neutrophils ≥ 1500/mm³ and platelets ≥80.000/mm³) -Ability to comply with the protocol procedures -Ability to take oral medication
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E.4 | Principal exclusion criteria |
-Large or small cell-poorly differentiated neuroendocrine carcinoma according to WHO 2000 classification -History of prior malignancy, -Severe renal or hepatic insufficiency -Patients with cardiac events -Hypertension -Brain metastases -Previous treatment with the drug under study. Prior systemic treatment with any tyrosine kinase inhibitors or anti VEGF angiogenic inhibitors. -Major surgery for any cause or local radiotherapy within one month prior to visit 1 -Liver embolisation therapy within the last 3 months prior visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival at 12 months. Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression-free survival at 12 months.
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E.5.2 | Secondary end point(s) |
-Objective Response Rates (ORR) -Duration of response (DR) -Overall Progression-free survival (PFS) -Overall Time to Progression (TTP) -Overall survival (OS) -Toxicity (NCI –CTC V4 criteria) -Cardiovascular tolerance assessed by specific organisation for blood pressure monitoring
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
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 | 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 | 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 | 4 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
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 |