Table 1.
Compilation of the VHL interventional clinical trials registered at the EU Clinical Trials Register (EudraCT) (https://www.clinicaltrialsregister.eu) and the U.S. National Library of Medicine (NCT) (https://clinicaltrials.gov). Only interventional trials whether a therapeutic drug was tested are listed. All the trials showed here were designed as single-arm, open-label trials. Abbreviations: Status: C (Completed); R (Recruiting); O (Ongoing); T (Terminated).
| Trial Registration |
Phase | Title | Intervention | Number of Patients | Status Start Date | Outcome | Link to Results |
|---|---|---|---|---|---|---|---|
| NCT00052013 | 2 | Treatment of Von Hippel-Lindau (VHL)-Related Hemangioblastoma With PTK787/ZK 222584 | PTK787 ZK 222584 (vatalanib) |
11 | C Feb 2003 |
100% discontinued (adverse events). |
[21] |
| NCT00056199 | 1 | EYE001 to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome |
EYE001(anti-VEGF aptamer) | 5 | C Mar 2003 |
80% showed stabilization or improvement of vision. | [22] |
| NCT00088374 | 2 | 17AAG to Treat Kidney Tumors in Von Hippel-Lindau Disease | 1 DMAG | 9 | C Jul 2004 |
Study did not meet accrual. | [23] |
| 18FDG | |||||||
| [15-O] H2O | |||||||
| EPL diluent | |||||||
| NCT00089765 | 1 | Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome | Ranibizumab | 5 | C Aug 2004 |
Not clear therapeutic effect. “Minimal beneficial effects on most VHL-related Retinal Capillary HB” | [24] |
| NCT00330564 | 2 | Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow | SU011248 (Sunitinib) |
15 | T May 2006 |
Early termination due to slow accrual. 33% showed partial response in RCC but not in HB. | [25,26] |
| NCT00470977 | 1/2 | Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy | Ranibizumab injection (0.5 mg) |
18 | C May 2007 |
- | - |
| EudraCT 2007-002132-29 |
2 | A Phase II Trial of Sorafenib (a tyrosine kinase inhibitor) given orally twice daily in renal cancer patients with vHL syndrome | Sorafenib | 25 | T Jan 2008 |
- | - |
| NCT00566995 | 2 | Phase II Study of Vandetanib in Individuals With Kidney Cancer | ZACTIMA (Vandetanib) (ZD6474) |
37 | C Feb 2008 |
80% completed the study. None of them showed a complete response and 8% showed a partial response. | [27] |
| NCT00673816 | 1/2 | Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome | Sunitinib Malate |
2 | T May 2008 |
Study did not meet accrual plus adverse events. | [28,29] |
| NCT01015300 | 1 | Bevacizumab (Avastin) in Unresectable/Recurrent Hemangioblastoma From VonHippel-Lindau Disease | Avastin | 1 | T Dec 2009 |
Study did not meet accrual. | - |
|
NCT01168440 EudraCT 2009-013052-76 |
2 | A single-arm, phase II study of SU11248 (sunitinib) in patients with von Hippel-Lindau (VHL) disease | Sunitinib | 5 | C Feb 2010 |
Disease progression (20%), unacceptable toxicity (60%), and lack of clinical improvement. after 7 cycles | [30] |
| EudraCT 2005-004502-82 |
2 | A Phase II Study of Neoadjuvant Sunitinib in Metastatic Renal Cell Carcinoma | Sunitinib | 16 | T Oct 2010 |
Study did not meet accrual. 58% showed complete or partial response. | [31] |
| NCT01436227 | 2 | Pazopanib in Von Hippel-Lindau (VHL) Syndrome | Pazopanib | 32 | O Jan 2012 |
80% discontinued (progressive disease, loss of quality of life, or intolerance). 42% showed partial response and 55% a complete or partial response in ccRCC. | [15] |
| NCT01266070 | 2 | TKI 258 in Von Hippel-Lindau Syndrome (VHL) | Dovitinib | 6 | T Nov 2012 |
33% discontinued plus the trial met toxicity stopping rule. | [32,33] |
| EudraCT 2014-003671-30 |
3 | Therapeutic effect of propranolol in a series of patients with von Hippel-Lindau disease and retinal hemangioblastomas in short, medium and long term treatment. | Propranolol | 7 | C Oct 2014 |
28% showed partial response and 72% a stable disease. No serious adverse effects were recorded. | [19,20] |
| NCT02108002 | 1 | Effect of Vorinostat on Nervous System Hemangioblastomas in Von Hippel-Lindau Disease (Missense Mutation Only) | Vorinostat | 7 | C Apr 2014 |
- | - |
| NCT02859441 | 1/2 | A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab | Ranibizumab & E10030 (anti-PDGF pegylated aptamer) |
3 | C Aug 2016 |
- | - |
| NCT03108066 | 2 | PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma | PT2385 Tablets (HIF-2α inhibitor) |
4 | O May 2017 |
- | - |
| NCT03401788 | 2 | A Phase 2 Study of PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma | PT2977 (HIF-2α inhibitor) |
61 | C Mar 2018 |
27.9% showed partial response. | [34] |