Phase I study of oral metronomic NAVELBINE® and HEMANGIOL®combination for children and teenagers with refractory/relapsing solid tumors

Phase I study of oral metronomic NAVELBINE® and HEMANGIOL®combination for children and teenagers with refractory/relapsing solid tumors - PROVIN

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-001772-10-FR

Enrollment

Registered

2020-01-09

Start date

2020-02-14

Completion date

Unknown

Last updated

2024-09-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pediatric Solid tumor MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864

Interventions

Trade Name: Hémangiol Product Name: Propranolol Pharmaceutical Form: Oral solution Trade Name: Propranolol TEVA 40 mg Product Name: Propranolol Pharmaceutical Form: Tablet Trade Name: Navelbine caps

Eligibility

Sex/Gender

All

Inclusion criteria

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 - Age > 4 years and 70 or score OMS 6 months. - Adequate haematological function: neutrophil count = 1.0 x 10 9 /L, platelet count = 75 x 10 9 /L - Creatinine70 ml/mn/1.73 m2 - Liver function: Bilirubin 12 years must have a negative pregnancy test within 7 days before study treatment - Associated disease do not prevent patients to be included in the study - Written informed consent from patient, parents or legal guardian. - Able to comply with follow-up - Affiliated with French social health system - Patients must have recovered from the acute toxic effects of all prior therapy before enrolment into the study Are the trial subjects under 18? yes Number of subjects for this age range: 54 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - Absence of a wash out period of: Page 6 of 22 - 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, hypotention, decreased SF, ECG-anomalies) - Pregnancy or breast feeding - Known allergy to one of the compounds or their solvents

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary Objective: To determine the Maximal Tolerated Dose (MTD) of oral Navelbine® given thrice a week with daily oral propranolol;Secondary Objective: - to determine the dose limiting toxicities (DLT) and tolerance of treatment with single agent metronomic navelbine - To determine the toxicity and tolerance of treatment with oral metronomic vinorelbine and daily propranolol - To determine the recommended dose of both drugs ? To establish PK of oral Navelbine® given 3 times a week during of the first cycle of treatment and and in combination with propranolol during the second cycle. - To evaluate PFS after 2, 4, 6, 12 months in the entire study population and in each cohort during the extension phase - To determine Response Rates at after 2, 4, 6 and 12 months in the entire study population and in each cohort during the extension phase. - To evaluate OS after 6 and 12 months in the entire study population and in each cohort during the extension phase ;Primary end point(s): MTD will be evaluated during the first cycle of treatment (28 days) with the NCI-CTC v4.0 scale and defined as followed : · Grade 3 /4 Neutropenia de grade 3 ou 4 with a delay of treatment of 7 days or more. · Grade 3 /4 Thrombocytopenia requiring blood support for 7 days or more. · Grade 3 /4 non hematological toxicity except : ? Nausea/vomiting despite adequate supportive care, ? Reversible Grade 3 fever and grade 3 hepatic toxicity ? Grade 3 bradycardia;Timepoint(s) of evaluation of this end point: 1 month	—

Measure

Time frame

Main Objective: Primary Objective: To determine the Maximal Tolerated Dose (MTD) of oral Navelbine® given thrice a week with daily oral propranolol;Secondary Objective: - to determine the dose limiting toxicities (DLT) and tolerance of treatment with single agent metronomic navelbine - To determine the toxicity and tolerance of treatment with oral metronomic vinorelbine and daily propranolol - To determine the recommended dose of both drugs ? To establish PK of oral Navelbine® given 3 times a week during of the first cycle of treatment and and in combination with propranolol during the second cycle. - To evaluate PFS after 2, 4, 6, 12 months in the entire study population and in each cohort during the extension phase - To determine Response Rates at after 2, 4, 6 and 12 months in the entire study population and in each cohort during the extension phase. - To evaluate OS after 6 and 12 months in the entire study population and in each cohort during the extension phase ;Primary end point(s): MTD will be evaluated during the first cycle of treatment (28 days) with the NCI-CTC v4.0 scale and defined as followed : · Grade 3 /4 Neutropenia de grade 3 ou 4 with a delay of treatment of 7 days or more. · Grade 3 /4 Thrombocytopenia requiring blood support for 7 days or more. · Grade 3 /4 non hematological toxicity except : ? Nausea/vomiting despite adequate supportive care, ? Reversible Grade 3 fever and grade 3 hepatic toxicity ? Grade 3 bradycardia;Timepoint(s) of evaluation of this end point: 1 month

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Secondary

Measure	Time frame
Secondary end point(s): - PK will be performed using liquid chromatography coupled with mass spectometry (LCMS/MS) for Navelbine® and liquid chromatography and UV detection for Hémangiol® - Efficacy: EFS will be evaluated from entry into the study to the date of progression or death (if related to the tumors or toxicity of treatment. Response Rate will be evaluated according to the RECIST criteria or with specific validated criteria for some tumors (i.e.RANO, INCR);Timepoint(s) of evaluation of this end point: 12 months	—

Measure

Time frame

Secondary end point(s): - PK will be performed using liquid chromatography coupled with mass spectometry (LCMS/MS) for Navelbine® and liquid chromatography and UV detection for Hémangiol® - Efficacy: EFS will be evaluated from entry into the study to the date of progression or death (if related to the tumors or toxicity of treatment. Response Rate will be evaluated according to the RECIST criteria or with specific validated criteria for some tumors (i.e.RANO, INCR);Timepoint(s) of evaluation of this end point: 12 months

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Countries

France

Contacts

Public ContactDirection de la Recherche Santé

Assistance Publique-Hôpitaux de Marseille

promotion.interne@ap-hm.fr

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026