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

September 12, 2016 updated by: Assistance Publique Hopitaux De Marseille

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

54

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13005
        • Assistance Publique Hopitaux de Marseille

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 17 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patients with refractory/relapsing solid tumors
Drug: administration of a propranolol (HEMANGIOL®) and oral metronomic vinorelbine (NAVELBINE®) combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
number of patients with grade 3 toxicity
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique Hopitaux De Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Anticipated)

January 1, 2020

Study Completion (Anticipated)

January 1, 2021

Study Registration Dates

First Submitted

September 8, 2016

First Submitted That Met QC Criteria

September 12, 2016

First Posted (Estimate)

September 13, 2016

Study Record Updates

Last Update Posted (Estimate)

September 13, 2016

Last Update Submitted That Met QC Criteria

September 12, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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