A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations

NCT05983159 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 85218
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Recent studies have demonstrated that growth of vascular malformations can be driven by genetic variants in one of 2 signalling pathways. Targeted drugs specific to these pathways have been developed and shown to be effective in treating cancer. This study will describe the effectiveness of (i) 48 weeks of alpelisib therapy for participants with slow-flow vascular malformations and a gene mutation in one of these signalling pathways (module 1) and (ii) 48 weeks of mirdametinib therapy for participants with fast-flow vascular malformations and a gene mutations in the other signalling pathway (module 2).

Conditions

Fast-Flow Vascular Malformation; Slow-Flow Vascular Malformation; Venous Malformation; Lymphatic Malformation, Low Flow; Lymphatic Malformation; Lymphangioma; Arteriovenous Malformations; Venous Malformation, Low Flow; Vascular Anomaly; Vascular Anomalies; PI3K Gene Mutation; MAP2K1 Gene Mutation; Vascular Malformations; Cystic Hygroma; PIK3CA-related Overgrowth Spectrum; Arteriovenous Malformation (AVM); KRAS G12C; KRAS G12D

Keywords

Targeted therapy; vascular malformations; skin diseases, vascular; Phosphatidylinositol 3-Kinases; MEK inhibitor 1

Outcome Measures

Primary Outcomes (1)

• The number of participants who achieve or exceed a predetermined threshold of improvement in their most significant symptom at 48 weeks based on the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM).

  Vascular malformations present with a range of different symptoms. Therefore, there is no single outcome measure that can capture the effectiveness of a systemic treatment across different patients. Thus for this study, an individualised primary outcome for each patient informed by their symptoms will be used, termed the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM). The study "Outcome Committee" will define an individualised primary outcome for each patient informed by their symptoms and vascular malformation features prior to starting trial treatments. The VM-PSOM endpoint will therefore define a binary outcome for each patients (achieved or failed to reach the threshold improvement in the chosen measure).

  At 48 weeks

Secondary Outcomes (5)

• The number of participants who achieve or exceed a predetermined threshold of improvement in their most significant symptom at the 168-day timepoint based on the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM).

  48 weeks, 168-day follow-up

• The number of participants with an objective response (defined as ≥ 20% reduction from index date in the sum of measurable target lesion volume) by volumetric analysis on MRI.

  Baseline, 48 weeks

• Change in symptoms score as recorded on the OVAMA (Outcome measures for VAscular MAlformations) questionnaire.

  Time frame: Baseline, 48 weeks

• Change in symptoms score as recorded on the OVAMA (Outcome measures for VAscular MAlformations) which is a set of questions developed specifically to measure symptom burden from vascular malformations.

  Time frame: 48 weeks, Day 168 follow-up

• The number of patients who experience adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.

  From Baseline to Day 168 follow-up

Study Arms (2)

Module 1: Slow-flow vascular malformations

EXPERIMENTAL

Slow-flow vascular malformations with identified causative variants in the phosphoinositide 3-kinase (PI3K) signalling pathway will receive alpelisib (provided by Novartis Pharmaceuticals), an oral alpha-specific PI3-kinase inhibitor for a total duration of 48 weeks as monotherapy, followed by 24 weeks of follow-up.

Drug: Alpelisib

Module 2: Fast-flow vascular malformations

EXPERIMENTAL

Fast-flow vascular malformations with identified causative variants in the RAS-MEK-ERK signalling pathway will receive mirdametinib (provided by SpringWorks Therapeutics, Inc.), an investigational oral MEK inhibitor for a total duration of 48 weeks as monotherapy, followed by 24 weeks of follow-up.

Drug: Mirdametinib

Interventions

Alpelisib DRUG

Oral alpha-specific PI3-kinase inhibitor

Also known as: BYL719

Module 1: Slow-flow vascular malformations

Mirdametinib DRUG

An investigational oral MEK inhibitor

Module 2: Fast-flow vascular malformations

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult or paediatric patient, 2 years of age or over
• Patient has a clinical diagnosis of a slow-flow vascular malformation
• Patient has received standard therapy for the vascular malformation or in which, in the opinion of the investigator, standard therapy is not appropriate
• \- Note: standard therapy may include treatment with sirolimus. A minimum of 14 days since the last dose of sirolimus is required prior to starting treatment with alpelisib
• A documented genetic alteration in the PI3K signalling pathway identified by genetic sequencing prior to enrolment in this study
• Adequate performance status (Eastern Cooperative Oncology Group Performance Status Scale (ECOG) 0-2 in patients ≥ 16 years of age; Lansky \> 50 in patients \< 16 years of age)
• Patient has a life expectancy ≥ 12 weeks
• Patient is able to swallow and retain oral medication
• Adequate haematologic and end-organ function:
• Haematology: Haemoglobin ≥ 9.0 g/dL; Absolute neutrophil count ≥ 1.5 x 109/L; Platelets ≥ 90 x 109/L, except where bleeding leading to low haemoglobin level is an indication for treatment, in which case haemoglobin \< 9.0 g/dL is acceptable.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AT) ≤ 3 x ULN; Total bilirubin \< 2x ULN except for participants with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
• Renal function: Serum creatinine \< 1.5 x ULN
• Biochemistry: Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ Grade 1 according to NCI-CTCAE v5.0 if judged clinically not significant by the investigator; Potassium within normal limits, or corrected with supplements
• Fasting blood glucose ≤ 7.0 mmol/L and Glycosylated Haemoglobin (HbA1c) ≤ 6.4% (both criteria must be met)
• Patient agrees to abstinence or highly effective contraceptive measures for males and women of childbearing potential (WOCBP)

You may not qualify if:

• History of hypersensitivity to any drugs or metabolites of PI3K inhibitors or any of the excipients of alpelisib
• Severe infection requiring intravenous antibiotics within 4 weeks prior to enrolment
• Patient has had a major surgical procedure within 4 weeks prior to enrolment
• Prior use of an alpha-specific PI3K inhibitor
• History of pneumonitis or interstitial lung disease
• Patient is pregnant or lactating at the time of study registration. A pregnancy test is mandated for women of child-bearing potential in the screening period
• Established diagnosis of type I diabetes mellitus, type II diabetes mellitus requiring anti-hyperglycaemic medication or any participant with HbA1c \> 6.4%
• Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes
• Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of treatment:
• Strong inducers of CYP3A4
• Strong inhibitors of CYP3A4
• Inhibitors of BCRP
• History of acute pancreatitis within 1 year of screening or past history of chronic pancreatitis
• Patient with Child Pugh score B or C
• Unresolved osteonecrosis of the jaw

Sponsors & Collaborators

• Royal Children's Hospital: collaborator
• Murdoch Childrens Research Institute: lead
• Peter MacCallum Cancer Centre, Australia: collaborator

Study Sites (2)

Peter MacCallum Cancer Centre

Parkville, Victoria, 3052, Australia

RECRUITING

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Related Publications (32)

• Garzon MC, Huang JT, Enjolras O, Frieden IJ. Vascular malformations: Part I. J Am Acad Dermatol. 2007 Mar;56(3):353-70; quiz 371-4. doi: 10.1016/j.jaad.2006.05.069.

  PMID: 17317485 BACKGROUND

• Penington, A.P., R.; Sleebs, N.; Halliday, J. , Epidemiology of Vascular Malformations Poster, in International Society for the Study of Vascluar Anomalies World Congress. 2022: Vancouver, British Columbia, Canada.

  BACKGROUND

• Wagner KM, Lokmic Z, Penington AJ. Prolonged antibiotic treatment for infected low flow vascular malformations. J Pediatr Surg. 2018 Apr;53(4):798-801. doi: 10.1016/j.jpedsurg.2017.05.022. Epub 2017 May 27.

  PMID: 28599969 BACKGROUND

• Cheng J, Liu B, Farjat AE, Routh J. The Public Health Burden of Lymphatic Malformations in Children: National Estimates in the United States, 2000-2009. Lymphat Res Biol. 2017 Sep;15(3):241-245. doi: 10.1089/lrb.2017.0009. Epub 2017 Jul 31.

  PMID: 28759318 BACKGROUND

• Liu AS, Mulliken JB, Zurakowski D, Fishman SJ, Greene AK. Extracranial arteriovenous malformations: natural progression and recurrence after treatment. Plast Reconstr Surg. 2010 Apr;125(4):1185-1194. doi: 10.1097/PRS.0b013e3181d18070.

  PMID: 20335868 BACKGROUND

• Chen RJ, Vrazas JI, Penington AJ. Surgical Management of Intramuscular Venous Malformations. J Pediatr Orthop. 2021 Jan;41(1):e67-e73. doi: 10.1097/BPO.0000000000001667.

  PMID: 32815867 BACKGROUND

• Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.

  PMID: 18550886 BACKGROUND

• Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, Dasgupta R, Azizkhan RG, Adams DM. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer. 2011 Dec 1;57(6):1018-24. doi: 10.1002/pbc.23124. Epub 2011 Mar 28.

  PMID: 21445948 BACKGROUND

• Adams DM, Trenor CC 3rd, Hammill AM, Vinks AA, Patel MN, Chaudry G, Wentzel MS, Mobberley-Schuman PS, Campbell LM, Brookbank C, Gupta A, Chute C, Eile J, McKenna J, Merrow AC, Fei L, Hornung L, Seid M, Dasgupta AR, Dickie BH, Elluru RG, Lucky AW, Weiss B, Azizkhan RG. Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies. Pediatrics. 2016 Feb;137(2):e20153257. doi: 10.1542/peds.2015-3257. Epub 2016 Jan 18.

  PMID: 26783326 BACKGROUND

• Hammer J, Seront E, Duez S, Dupont S, Van Damme A, Schmitz S, Hoyoux C, Chopinet C, Clapuyt P, Hammer F, Vikkula M, Boon LM. Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study. Orphanet J Rare Dis. 2018 Oct 29;13(1):191. doi: 10.1186/s13023-018-0934-z.

  PMID: 30373605 BACKGROUND

• Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, Parker VE, Blumhorst C, Darling T, Tosi LL, Huson SM, Whitehouse RW, Jakkula E, Grant I, Balasubramanian M, Chandler KE, Fraser JL, Gucev Z, Crow YJ, Brennan LM, Clark R, Sellars EA, Pena LD, Krishnamurty V, Shuen A, Braverman N, Cunningham ML, Sutton VR, Tasic V, Graham JM Jr, Geer J Jr, Henderson A, Semple RK, Biesecker LG. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A. 2014 Jul;164A(7):1713-33. doi: 10.1002/ajmg.a.36552. Epub 2014 Apr 29.

  PMID: 24782230 BACKGROUND

• Venot Q, Blanc T, Rabia SH, Berteloot L, Ladraa S, Duong JP, Blanc E, Johnson SC, Hoguin C, Boccara O, Sarnacki S, Boddaert N, Pannier S, Martinez F, Magassa S, Yamaguchi J, Knebelmann B, Merville P, Grenier N, Joly D, Cormier-Daire V, Michot C, Bole-Feysot C, Picard A, Soupre V, Lyonnet S, Sadoine J, Slimani L, Chaussain C, Laroche-Raynaud C, Guibaud L, Broissand C, Amiel J, Legendre C, Terzi F, Canaud G. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546. doi: 10.1038/s41586-018-0217-9. Epub 2018 Jun 13.

  PMID: 29899452 BACKGROUND

• Canaud, G., et al., LBA23 EPIK-P1: Retrospective chart review study of patients (pts) with PIK3CA-related Overgrowth Spectrum (PROS) who have received alpelisib (ALP) as part of a compassionate use programme. Annals of Oncology, 2021. 32: p. S1297.

  BACKGROUND

• Al-Olabi L, Polubothu S, Dowsett K, Andrews KA, Stadnik P, Joseph AP, Knox R, Pittman A, Clark G, Baird W, Bulstrode N, Glover M, Gordon K, Hargrave D, Huson SM, Jacques TS, James G, Kondolf H, Kangesu L, Keppler-Noreuil KM, Khan A, Lindhurst MJ, Lipson M, Mansour S, O'Hara J, Mahon C, Mosica A, Moss C, Murthy A, Ong J, Parker VE, Riviere JB, Sapp JC, Sebire NJ, Shah R, Sivakumar B, Thomas A, Virasami A, Waelchli R, Zeng Z, Biesecker LG, Barnacle A, Topf M, Semple RK, Patton EE, Kinsler VA. Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy. J Clin Invest. 2018 Apr 2;128(4):1496-1508. doi: 10.1172/JCI98589. Epub 2018 Mar 12.

  PMID: 29461977 BACKGROUND

• Dombi E, Ardern-Holmes SL, Babovic-Vuksanovic D, Barker FG, Connor S, Evans DG, Fisher MJ, Goutagny S, Harris GJ, Jaramillo D, Karajannis MA, Korf BR, Mautner V, Plotkin SR, Poussaint TY, Robertson K, Shih CS, Widemann BC; REiNS International Collaboration. Recommendations for imaging tumor response in neurofibromatosis clinical trials. Neurology. 2013 Nov 19;81(21 Suppl 1):S33-40. doi: 10.1212/01.wnl.0000435744.57038.af.

  PMID: 24249804 BACKGROUND

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Matthews HS, Penington AJ, Hardiman R, Fan Y, Clement JG, Kilpatrick NM, Claes PD. Modelling 3D craniofacial growth trajectories for population comparison and classification illustrated using sex-differences. Sci Rep. 2018 Mar 19;8(1):4771. doi: 10.1038/s41598-018-22752-5.

  PMID: 29556038 BACKGROUND

• Fan Y, Penington A, Kilpatrick N, Hardiman R, Schneider P, Clement J, Claes P, Matthews H. Quantification of mandibular sexual dimorphism during adolescence. J Anat. 2019 May;234(5):709-717. doi: 10.1111/joa.12949. Epub 2019 Mar 4.

  PMID: 30834524 BACKGROUND

• Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad AR, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain. 2003 Dec;106(3):337-345. doi: 10.1016/j.pain.2003.08.001.

  PMID: 14659516 BACKGROUND

• Patel KV, Amtmann D, Jensen MP, Smith SM, Veasley C, Turk DC. Clinical outcome assessment in clinical trials of chronic pain treatments. Pain Rep. 2021 Jan 21;6(1):e784. doi: 10.1097/PR9.0000000000000784. eCollection 2021 Jan-Feb.

  PMID: 33521482 BACKGROUND

• Stinson JN, Kavanagh T, Yamada J, Gill N, Stevens B. Systematic review of the psychometric properties, interpretability and feasibility of self-report pain intensity measures for use in clinical trials in children and adolescents. Pain. 2006 Nov;125(1-2):143-57. doi: 10.1016/j.pain.2006.05.006. Epub 2006 Jun 13.

  PMID: 16777328 BACKGROUND

• Younger J, McCue R, Mackey S. Pain outcomes: a brief review of instruments and techniques. Curr Pain Headache Rep. 2009 Feb;13(1):39-43. doi: 10.1007/s11916-009-0009-x.

  PMID: 19126370 BACKGROUND

• Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, Rowbotham MC, Bhagwagar Z, Burke LB, Cowan P, Ellenberg SS, Evans SR, Freeman RL, Garrison LP, Iyengar S, Jadad A, Jensen MP, Junor R, Kamp C, Katz NP, Kesslak JP, Kopecky EA, Lissin D, Markman JD, Mease PJ, O'Connor AB, Patel KV, Raja SN, Sampaio C, Schoenfeld D, Singh J, Steigerwald I, Strand V, Tive LA, Tobias J, Wasan AD, Wilson HD. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020 Nov;161(11):2446-2461. doi: 10.1097/j.pain.0000000000001952.

  PMID: 32520773 BACKGROUND

• Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN; REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. doi: 10.1016/j.jbi.2019.103208. Epub 2019 May 9.

  PMID: 31078660 BACKGROUND

• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.

  PMID: 18929686 BACKGROUND

• Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, Maira SM, Wilson C, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens R, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR. Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29. doi: 10.1158/1535-7163.MCT-13-0865. Epub 2014 Mar 7.

  PMID: 24608574 BACKGROUND

• Janku F, Hong DS, Fu S, Piha-Paul SA, Naing A, Falchook GS, Tsimberidou AM, Stepanek VM, Moulder SL, Lee JJ, Luthra R, Zinner RG, Broaddus RR, Wheler JJ, Kurzrock R. Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors. Cell Rep. 2014 Jan 30;6(2):377-87. doi: 10.1016/j.celrep.2013.12.035. Epub 2014 Jan 16.

  PMID: 24440717 BACKGROUND

• Anderson NG, Maller JL, Tonks NK, Sturgill TW. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature. 1990 Feb 15;343(6259):651-3. doi: 10.1038/343651a0.

  PMID: 2154696 BACKGROUND

• Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012 Aug;66(2):105-43. doi: 10.1016/j.phrs.2012.04.005. Epub 2012 Apr 27.

  PMID: 22569528 BACKGROUND

• Hoshino R, Chatani Y, Yamori T, Tsuruo T, Oka H, Yoshida O, Shimada Y, Ari-i S, Wada H, Fujimoto J, Kohno M. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene. 1999 Jan 21;18(3):813-22. doi: 10.1038/sj.onc.1202367.

  PMID: 9989833 BACKGROUND

• Weiss BD, Wolters PL, Plotkin SR, Widemann BC, Tonsgard JH, Blakeley J, Allen JC, Schorry E, Korf B, Robison NJ, Goldman S, Vinks AA, Emoto C, Fukuda T, Robinson CT, Cutter G, Edwards L, Dombi E, Ratner N, Packer R, Fisher MJ. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. J Clin Oncol. 2021 Mar 1;39(7):797-806. doi: 10.1200/JCO.20.02220. Epub 2021 Jan 28.

  PMID: 33507822 BACKGROUND

MeSH Terms

Conditions

Vascular Malformations; Lymphatic Abnormalities; Lymphangioma; Arteriovenous Malformations; Lymphangioma, Cystic; Skin Diseases, Vascular

Interventions

Alpelisib; mirdametinib

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Vascular Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Tony Penington, MBBS, FRACS.

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

• Stephen Luen, MBChB, FRACP.

  Principal Investigator

  PRINCIPAL INVESTIGATOR

• Lydia Pathmanathan, MBBS, FRACP.

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle de Silva, PhD

CONTACT

+61399366109; michelle.desilva@vcgs.org.au

Tony Penington, MBBS, FRACS

CONTACT

+61383416200; tony.penington@rch.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: i) Participants with slow-flow vascular malformations with an eligible gene mutation will receive 48 weeks of treatment with open-label alpelisib. ii) Participants with fast-flow vascular malformations with an eligible gene mutation will receive 48 weeks of treatment with open-label mirdametinib

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 9, 2023
• Study Start: September 13, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Available from 6 months following analysis and article publication
• Access Criteria: Future researchers must be from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access

Locations

AU (2)