Study of a Propranolol (HEMANGIOL®) and Oral Metronomic Vinorelbine (NAVELBINE®) Combination for Children and Teenagers With Refractory/Relapsing Solid Tumors

NCT02897986 | Unknown Phase 1

• 1 other identifier: 2016-06
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pediatric Cancer

Outcome Measures

Primary Outcomes (1)

• number of patients with grade 3 toxicity

  28 days

Study Arms (1)

patients with refractory/relapsing solid tumors

EXPERIMENTAL

Drug: administration of a propranolol (HEMANGIOL®) and oral metronomic vinorelbine (NAVELBINE®) combination

Interventions

administration of a propranolol (HEMANGIOL®) and oral metronomic vinorelbine (NAVELBINE®) combination DRUG

patients with refractory/relapsing solid tumors

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Absence of a wash out period of:
• 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)
• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13005, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Vinorelbine

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Urielle Desalbres

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Central Study Contacts

Nicolas ANDRE, Professor

CONTACT

nicolas.andre@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 13, 2016
• Study Start: January 1, 2017
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2021
• Last Updated: September 13, 2016

Record last verified: 2016-09

Locations

FR (1)