Neoadjuvant β-blocker in angiosarcoma patients

Neoadjuvant β-blocker in angiosarcoma patients

Neoadjuvant trial on the efficacy of propranolol monotherapy in patients with cutaneous angiosarcoma (PropAngio). 

Status
Recruiting
Cancer types
  • Sarcoma
Trial phase
2

Funding

€169,447.50
ACF donation
€187,977.50
Estimated trial cost

Why this trial?

Angiosarcoma is an aggressive and rare cancer type with a high risk of spreading (i.e. developing metastases). The standard treatment for localised angiosarcoma is to surgically remove the entire tumour, sometimes combined with radiation. However, despite optimal disease management approximately half of patients relapse.

Although the role of chemotherapy before or after surgery remains controversial for localised disease, neoadjuvant chemotherapy (before surgery) is often administered for locally advanced angiosarcoma. Several chemotherapies have shown activity in the locally advanced and metastatic setting but none have shown a beneficial effect in terms of prolonged survival or time to relapse when used in a neoadjuvant fashion among patients with operable angiosarcoma. 

By improving the neoadjuvant treatment of this disease and effectively treating micro-metastases at an early stage, the number of local and distant recurrences might be reduced, potentially leading to higher survival rates. New drugs for the neoadjuvant setting for angiosarcoma are thus urgently needed. 

Why this drug?

Propranolol, a β-blocker, has recently been repurposed against a benign vascular tumour called haemangioma with 88% complete or near complete resolution of the treated lesions. Haemangiomas express high levels of β-adrenergic receptors potentially explaining their sensitivity to propranolol. These receptors are reported to be highly expressed in malignant vascular tumours suggesting the effect of propranolol and other β-blockers may extend to aggressive vascular tumours like angiosarcoma as well.

Several case reports have indeed suggested that propranolol could be repurposed to treat angiosarcoma. Patients with locally advanced or metastatic angiosarcoma have been treated with propranolol in combination with various chemotherapies. Also, a reduction in proliferation index and stabilisation of tumour growth of angiosarcoma in response to propranolol monotherapy has been reported in one patient.

Propranolol is an already approved drug with well-known pharmacokinetic properties and toxicity profile, and has been or is being used in more than 20 oncology trials, including one trial in advanced angiosarcoma.

Trial design

This is a single-arm neoadjuvant window of opportunity phase II study to explore the activity of propranolol in cutaneous angiosarcoma. Propranolol will be administered as monotherapy in a dose of 40-80 mg 2-3 times a day, if tolerated. 14 patients with newly diagnosed, recurrent or metastatic cutaneous angiosarcoma (including angiosarcoma of the breast) will be recruited. 

Partners

Researchers: 

  • Winan van Houdt, The Netherlands Cancer Institute, Amsterdam, The Netherlands (Coordinating Investigator)
  • Neeltje Steeghs, The Netherlands Cancer Institute, Amsterdam, The Netherlands (Principal Investigator) 

Sponsor: 

  • The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL)

ACF co-funding partners:

  • Ockier & Partners Advocaten
  • Vansteelandt BV - Plan 3D

Our role

Fincancial support
Why we support this trial
Profit is a low priority in cancer treatment for the Anticancer Fund
Intervention has little or no commercial value
The Anticancer Fund wants to maximize the benefit for cancer patients
Expected survival benefit
The Anticancer Fund aims at no major hurdle for clinical implementation
No major hurdle for clinical implementation
The Anticancer Fund supports a trial that benefits a population with high unmet needs
Benefits a population with high unmet needs

Funding

€187,977.50
Estimated trial cost
€169,447.50
ACF donation
€9,873.00
ACF internal support (2019)
Questions about participation?
Alaa Embaby
Questions about this trial?
The Anticancer Fund
studies [at] anticancerfund.org

References

More info: NL71090.031.19

Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L, Baselga E, Posiunas G, et al. A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma. N Engl J Med [Internet]. 2015 [cited 2018 Nov 6];372:735–46. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1404710 

Léauté-Labrèze C, de la Roque ED, Hubiche T, Boralevi F, Thambo J-B, Taïeb A. Propranolol for Severe Hemangiomas of Infancy. N Engl J Med [Internet]. 2008 [cited 2018 Mar 28];358:2649–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18550886 

Daguzé J, Saint-Jean M, Peuvrel L, Cassagnau E, Quéreux G, Khammari A, et al. Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. JAAD Case Reports [Internet]. 2016 [cited 2018 Nov 6];2:497–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2352512616301230 

Pasquier E, André N, Street J, Chougule A, Rekhi B, Ghosh J, et al. Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine [Internet]. 2016 [cited 2018 Nov 6];6:87–95. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2352396416300652 

Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, Bryan BA. Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade. JAMA dermatology [Internet]. 2015 [cited 2018 Mar 28];151:1226–9. Available from: http://archderm.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.20...

Heinhuis KM, IJzerman NS, Koenen AM, et al. PropAngio study protocol: a neoadjuvant trial on the efficacy of propranolol monotherapy in cutaneous angiosarcoma—a proof of principle study. BMJ Open 2020;10:e039449. doi:10.1136/bmjopen-2020-039449
https://bmjopen.bmj.com/content/10/9/e039449

Author: Kristine Beckers (Trial Manager)

Last updated: September 2020