E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
von Hippel-Lindau (VHL) disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047716 |
E.1.2 | Term | Von Hippel-Lindau disease |
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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 determine the objective response rate in VHL patients with advanced or untreatable tumors after initiation of treatment with sunitinib |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the safety and tolerability of sunitinib in VHL patients according to the NCI-CTC criteria Version 3.0. 2) To determine time-to-event variables of survival, time to disease progression, time to response and duration of response. 3) To evaluate quality of life in VHL patients receiving sunitinib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must have genetically or clinically confirmed VHL disease and have symptoms from VHL that are no longer controllable by conventional approaches. 2. Patients must have at least one of the following lesions : • Eye : retinal hemangioblastoma that can no longer be treated by laser therapy or cryotherapy and resulting in progressive loss of vision; • CNS : cerebellar, bulbar, spinal, or cerebellopontine angle haemangioblastoma or endolymphatic sac tumor causing neurological symptoms that are not amenable to further surgery, or have recurred after a first surgery; • Kidney: multiple or bilateral tumors not accessible to conservative surgery, or tumors having recurred after surgery and/or radiofrequency ablation or advanced/metastatic RCC;. • Pancreas: inextirpable or advanced neuroendocrine tumors. 3. Patients previously treated for VHL with surgery, chemotherapy or radiotherapy are considered eligible for this study under the condition that these treatments were completed more than 4 weeks prior starting the study treatment. Previously radiated lesions will be considered as target lesions only if they demonstrate unequivocal evidence of growth upon imagery. 4. Male or female, at least 18 year-old. 5. Performance status ECOG 0-2 6. Life expectancy 3 months
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E.4 | Principal exclusion criteria |
1. Chemotherapy, radiotherapy, radiofrequency or surgery within 4 weeks prior to entering the study or not complete recovering from adverse events due to drugs administered more than 4 weeks earlier. 4. Previous treatment with sunitinib 5. NCI-CTCAE grade 3 hemorrhage within 4 weeks prior to study entry. 6. History of known or suspected brain metastases, spinal cord compression, carcinomatous meningitis, evidence of leptomeningeal disease (excepted leptomeningeal hemangioblastoma, according to the neurologist) on screening CT scan or MRI. 7. Any of the following within the 6 months prior to study drug administration: symptomatic congestive heart failure, myocardial infarction or coronary artery bypass, pulmonary embolism, ongoing severe or unstable angina pectoris, NCI-CTCAE grade 2 cardiac dysrhythmia, cerebrovascular accident or transient ischemic attack. 8. Hypertension >140/90 mmHg that cannot be controlled despite optimal antihypertensive therapy. 13. Pregnancy or breastfeeding. Patients must agree to use effective contraception during the study, including oral contraceptives, intrauterine devices, or being unable to procreate. 14. Any other malignancy within the last 3 years excepted basal cell carcinoma, in situ cervical carcinoma, squamous cell skin cancer, pT1/a bladder cancer with no evidence of recurrence during the last 12 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) defined as the fraction of patients having received at least one dose of sunitinib with confirmed responses (complete or partial) on measurable lesion(s) according to RECIST criteria v1.0. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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Disease progression or unacceptable toxicity |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |