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Dose-Finding of Propranolol in Combination With Metronomic Fixed Oral Cyclophosphamide Based on Bivariate Efficacy-tolerability Outcome in Patients With Locally Advanced or Metastatic Angiosarcoma: A Collaborative and Innovative Phase I-II Sequential Trial by the French Sarcoma Group (GSF/GETO)

NCT02732678 · Status: UNKNOWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2016-04-11

No results posted yet for this study

Summary

Adrenergic processes stimulated by epinephrine and norepinephrine drive to the development of tumor growth and metastasis. Beta-adrenergic receptor (BAR) antagonists have shown efficacy against melanoma, breast cancer and prostate cancer. The non-specific BAR inhibitor propranolol has been used as the gold standard treatment in pediatric patients with benign infantile hemangioma which express high levels of beta adrenergic receptors potentially explaining their sensitively to propranolol. BAR have been shown to be expressed across a diverse panel of vascular tumors, with the highest expression in malignant vascular tumors including angiosarcoma. Several reports indicate positive results from beta-blockade in patients with moderately threatening vascular tumors. It remains to be determined if more malignant vascular tumor such as the angiosarcomas are susceptible to propranolol. Besides, due to the lack of adequate therapies for angiosarcoma (doxorubicin or paclitaxel and finally cyclophosphamide in third line) and to the poor prognosis of this rare and aggressive tumor, there is a strong need for the development of treatments against this tumor type. Recently using a panel of angiosarcoma cell lines. demonstrate that beta-adrenergic inhibition blocks cell proliferation and induces apoptosis in a dose dependent manner. Moreover, using in vivo tumor models they demonstrate that propanolol shows remarkable efficacy in reducing the growth of angiosarcoma tumors. Based on these proofs of mechanisms in vitro and in vivo and due to the well established safety propranolol in humans, investigators propose to determine among a wide range of propranolol dose (80 mg/d ; 120 mg/d and 160 mg/d) the optimal one based on bivariate efficacy-toxicity outcome in patients with angiosarcoma treated by cyclophosphamide. Because these two drugs have different pharmacological mechanisms, the aim is to determine the optimal dose of propranolol having the best systemic cardiovascular tolerability and the best potential antiangiogenic effect in addition with cyclophosphamide.

Conditions

  • Angiosarcoma

Interventions

DRUG

PROPRANOLOL

Sponsors & Collaborators

  • Assistance Publique Hopitaux De Marseille

    lead OTHER

Principal Investigators

  • Urielle Desalbres · Assistance Publique Hôpitaux de Marseille

  • Sébatien SALAS, MD PhD · Assistance Publique Hôpitaux de Marseille

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
FACTORIAL

Eligibility

Min Age
15 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-05-31
Primary Completion
2018-05-31
Completion
2019-05-31

Countries

  • France

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02732678 on ClinicalTrials.gov