Patients presenting angiosarcomas disease
Conditions
Interventions
Trade Name: AVLOCARDYL 40mg
Product Name: AVLOCARDYL
Product Code: Propranolol
Pharmaceutical Form: Cachet
INN or Proposed INN: Chlorhydrate de Propranolol
Concentration unit: mg milligram(s)
Concentr
Sponsors
Assistance Publique Hôpitaux de MARSEILLE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Man or woman 18 years old or over and a World Health Organization performance status score = 2 PS; - Adolescents > 15 years with body surface > 1.6 m2 • Subject with an Histologically proven angiosarcoma, reviewed by an independent pathologist, with metastasis or locally advanced stage not amenable to radiotherapy or curative-intent surgery after multidisciplinary decision making; • Subject with Prior systemic treatment with paclitaxel or doxorubicin; • Subject with angiosarcoma with an indication and prescription of treatment by oral cyclophosphamide after multidisciplinary decision making; • Subject with no more than two prior lines of chemotherapy (whatever the indication); • Subjects with absence of brain or meningeal metastasis; • Subject with at least one lesion measurable according to the RECIST, version 1.1; • Subject with neutrophil count =1,000/mm3, platelet count = 100 000/mm3, hemoglobin level = 8 g/Dl, liver transaminases = 1.5 x ULN, total bilirubin = 1.5 x ULN, serum creatinine = 1.5 x ULN, and amylase and lipase = 1.5 x ULN. Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: • Minors or pregnant or breast-feeding women. • Subject with a contraindication to propranolol (ie cardiogenic shock; sinus bradycardia and greater than first-degree block; Chronic Obstructive Pulmonary Disease and bronchial asthma; patients with known hypersensitivity to Propranolol; assessed by cardiovascular and pulmonar history and examinations including blood pressure, ECG; untreated Pheochromocytoma, Congestive heart failure not controlled by treatment, Prinzmetal’s angina) • Subject with Severe Raynaud Phenomena or Raynaud Disease • Subject with Prior systemic treatment with Cyclophosphamide as 1st or 2nd line
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the optimal dose of propranolol (out of 80 mg/d; 120 mg/d and 160 mg/d) in terms of toxicity and efficacy assessed by non-progression rate at 3 months in patients with angiosarcomas treated by fixed dose of oral cyclophosphamide;Secondary Objective: The second objectives of this study are the following: - Response rate at 3, 6 and 9 months (according to RECIST 1.1 guidelines and after central radiological review) - Progression free survival (from the date of inclusion to the date of documented progression or date of last follow-up) - Growth modulation index (GMI=time to progression under study treatment divided by the time to progression under the prior treatment) - Overall survival (from the date to inclusion to the date of death or last follow-up) - Tolerability of combination propranolol and oral cyclophosphamide according to NCI-CTC AE Version 4.0 ;Primary end point(s): This dose-finding study will jointly model the toxicity and the efficacy as primary endpoints: - The toxicity of propranolol is well described on humans as well as its pharmacokinetic (Peak plasma concentrations occur about 1 to 4 hours) after oral dose and pharmacodynamics characteristics with the main target on beta-adrenergic receptor (blocking agent possessing no other autonomic nervous system activity). In this study the toxicity of each tested propranolol dose level in association to cyclophosphamide will be assessed according to NCI-CTC AE Version 4.0 at 1 month (Recording AE, Blood pressure, and electrocardiography). A dose-limiting toxicity (DLT) will be considered as any grade 3 or higher specially cardiac and hematologic but also non-hematologic toxicity that is probably or definitely related to treatment. - The efficacy criterion is defined as the non-progression rate at 3 months according to RECIST 1.1 guidelines and with central radiological review. ;Timepoint(s) of evaluation of this end point: Toxicity will be | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Response rate •Progression free survival •Growth modulation index •Overall survival •Tolerability ;Timepoint(s) of evaluation of this end point: •Response rate at 3, 6 and 9 months (according to RECIST 1.1 guidelines and after central radiological review) •Progression free survival Progression free survival will be defined from the date of inclusion to the date of documented progression or date of last follow-up. •Growth modulation index GMI will be defined by the time to progression under study treatment divided by the time to progression under the prior treatment •Overall survival Overall survival will be defined as the time from baseline evaluation until death due to any cause (linked or not to the disease). •Tolerability of combination propranolol and oral cyclophosphamide according to NCI-CTC AE Version 4.0 | — |
Countries
France
Contacts
Public ContactArnaud VANNESTE
Assistance Publique Hôpitaux de MARSEILLE
Outcome results
None listed