Informations générales (source: ClinicalTrials.gov)
(PROVIN)
Interventional
Phase 1
Assistance Publique Hopitaux De Marseille (Voir sur ClinicalTrials)
janvier 2017
janvier 2021
19 octobre 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:43 | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Assistance Publique Hôpitaux de Marseille - 13005 - Marseille - France | Nicolas ANDRE, Professor | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Histologically or cytologically confirmed malignant solid tumour and refractory low
grade gliomas and desmoids tumours.
- Relapsed or refractory tumours after at least one line of treatment (patients can
have been previously treated with oral or IV vinorelbine with a weekly schedule)
- Measurable targets
- Lansky Score > 70 or score OMS < 2.
- Life expectancy > 6 months.
- Adequate haematological function: neutrophil count ≥ 1.0 x 109/L, platelet count ≥
75 x 109/L
- Creatinine< 1.5X normal value for the age or clearance >70 ml/mn/1.73 m2
- Liver function: Bilirubin < 3N and ALAT and ASAT < 4 N).
- Other organ toxicity < Grade 2 according to NCI-CTC version 4.0
- No active infection
- Histologically or cytologically confirmed malignant solid tumour and refractory low
grade gliomas and desmoids tumours.
- Relapsed or refractory tumours after at least one line of treatment (patients can
have been previously treated with oral or IV vinorelbine with a weekly schedule)
- Measurable targets
- Lansky Score > 70 or score OMS < 2.
- Life expectancy > 6 months.
- Adequate haematological function: neutrophil count ≥ 1.0 x 109/L, platelet count ≥
75 x 109/L
- Creatinine< 1.5X normal value for the age or clearance >70 ml/mn/1.73 m2
- Liver function: Bilirubin < 3N and ALAT and ASAT < 4 N).
- Other organ toxicity < Grade 2 according to NCI-CTC version 4.0
- No active infection
- Absence of a wash out period of:
- 21 days in case of previous chemotherapy or targeted therapy (reduced to 2
weeks in case of treatment vincristine or prolonged to 6 weeks in case of
treatment with nitrosurea agents)
- 6 weeks in case of prior radiotherapy of the target lesions
- Peripheral neuropathy > grade 2
- contra-indication to Propranolol (i.e. asthma, bradycardia, hypotension, decreased
SF, ECG-anomalies)
- Pregnancy or breast feeding