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 | 14.1 |
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 | 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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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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Any patients still on study drug at the time overall survival results become available will be allowed to continue at the discretion of the investigator and provided the criteria for study drug
discontinuation are not met.
The study will stop 36 months after the randomization of the last patients. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |