Study of a Propranolol (HEMANGIOL®) and Oral Metronomic Vinorelbine (NAVELBINE®) Combination for Children and Teenagers With Refractory/Relapsing Solid Tumors (PROVIN)
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|ClinicalTrials.gov Identifier: NCT02897986|
Recruitment Status : Not yet recruiting
First Posted : September 13, 2016
Last Update Posted : September 13, 2016
Cancer remains the first cause of death due to disease in children and adolescents despite important progress and 70% of the survivors present sequelae. It is therefore mandatory to generate new and preferably less toxic treatment strategies relying on new anticancer agents, and/or new combinations or schedules of administered compounds.
Metronomic chemotherapy (MC) consists in administrating low doses of anticancer agents on a daily/weekly basis. MC has been showed to be a safe and effective way to administer chemotherapy to obtain anti-cancer effects through anti-angiogenic and pro-imune effects.
Drug repositioning consist in using non-anticancer drug for which anti-cancer properties have been unveiled. Propranolol is a non selective beta-blocker initially used to treat hypertension but recently its anticancer properties have been discovered. The place of Betablockers as anticancer agents is supported by both preclinical and epidemiologic data. The investigators have showed that the use of betablockers could sensitize breast cancer, angiosarcoma and neuroblastoma to chemotherapy in vitro and in vivo at least in part via an anti-angiogenic mechanism. There are currently 12 clinical trials evaluating prospectively their potential in adults with cancer but none in children so far.
The Objective is to determine the Maximal Tolerated Dose (MTD) of a combination of oral metronomic vinorelbine and daily oral propranolol. This study is a phase I trial with a "rolling six" design and a dose escalation with thrice weekly oral vinorelbine only plus addition of daily oral propranolol after completion of the first cycle. PK analysis of vinorelbine and propranolol will be performed. Once the recommended dose of the combination established 4 extension cohorts of 9 patients will be added Potential biomarkers (such as beta-adrenergic receptors on the tumours, B-tubulin isotypes in the tumour) will also be evaluated.
This will provide a well tolerated, all oral combination for patients with refractory/relapsing tumours. This combination could also be then proposed as a maintenance for instance in patients with rhabdomyosarcoma or neuroblastoma.
|Condition or disease||Intervention/treatment||Phase|
|Pediatric Cancer||Drug: administration of a propranolol (HEMANGIOL®) and oral metronomic vinorelbine (NAVELBINE®) combination||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Study Start Date :||January 2017|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2021|
|Experimental: patients with refractory/relapsing solid tumors||
Drug: administration of a propranolol (HEMANGIOL®) and oral metronomic vinorelbine (NAVELBINE®) combination
- number of patients with grade 3 toxicity [ Time Frame: 28 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02897986
|Contact: Nicolas ANDRE, Professorfirstname.lastname@example.org|
|Assistance Publique Hôpitaux de Marseille|
|Marseille, France, 13005|
|Contact: Nicolas ANDRE, Professor email@example.com|
|Study Director:||Urielle Desalbres||Assistance Publique Hôpitaux de Marseille|