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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05983159




Registration number
NCT05983159
Ethics application status
Date submitted
27/07/2023
Date registered
9/08/2023
Date last updated
27/09/2024

Titles & IDs
Public title
A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
Scientific title
A Modular Open Label, Signal Seeking, Phase II Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations (TARGET-VM)
Secondary ID [1] 0 0
85218
Universal Trial Number (UTN)
Trial acronym
TARGET-VM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Slow-Flow Vascular Malformation 0 0
Fast-Flow Vascular Malformation 0 0
Vascular Malformations 0 0
Venous Malformation 0 0
Lymphatic Malformation, Low Flow 0 0
Lymphatic Malformation 0 0
Lymphangioma 0 0
Arteriovenous Malformations 0 0
Venous Malformation, Low Flow 0 0
Cystic Hygroma 0 0
Vascular Anomaly 0 0
Vascular Anomalies 0 0
PI3K Gene Mutation 0 0
MAP2K1 Gene Mutation 0 0
PIK3CA-related Overgrowth Spectrum 0 0
Arteriovenous Malformation (AVM) 0 0
KRAS G12C 0 0
KRAS G12D 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alpelisib
Treatment: Drugs - Mirdametinib

Experimental: Module 1: Slow-flow vascular malformations - 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.

Experimental: Module 2: Fast-flow vascular malformations - 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.


Treatment: Drugs: Alpelisib
Oral alpha-specific PI3-kinase inhibitor

Treatment: Drugs: Mirdametinib
An investigational oral MEK inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
At 48 weeks
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
48 weeks, 168-day follow-up
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, 48 weeks
Secondary outcome [3] 0 0
Change in symptoms score as recorded on the OVAMA (Outcome measures for VAscular MAlformations) questionnaire.
Timepoint [3] 0 0
Time frame: Baseline, 48 weeks
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Time frame: 48 weeks, Day 168 follow-up
Secondary outcome [5] 0 0
The number of patients who experience adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.
Timepoint [5] 0 0
From Baseline to Day 168 follow-up

Eligibility
Key inclusion criteria
MODULE 1



1. Adult or paediatric patient, 2 years of age or over
2. Patient has a clinical diagnosis of a slow-flow vascular malformation
3. 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
4. A documented genetic alteration in the PI3K signalling pathway identified by genetic sequencing prior to enrolment in this study
5. 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)
6. Patient has a life expectancy = 12 weeks
7. Patient is able to swallow and retain oral medication
8. 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)
9. Patient agrees to abstinence or highly effective contraceptive measures for males and women of childbearing potential (WOCBP)

* Males who are sexually active must use a condom during intercourse while taking alpelisib and for at least 4 weeks after stopping alpelisib and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid. In addition, male participants must not donate sperm during the study and for at least 4 weeks after stopping alpelisib
* Females who are of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use a highly effective method of contraception during study treatment and for at least 1 week after the last dose of any study treatment. Highly effective contraceptive methods include:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject) Periodic abstinence (eg., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
* Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the women has been confirmed by follow up hormone level assessment;
* Male partner sterilisation (at least 6 months prior to screening) of the sole partner of a female participant on the study;
* Use of oral (estrogen and progesterone), injected or implanted combined hormonal method of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormonal vaginal ring or transdermal hormone contraception. In the case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
* Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhoea with an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of child bearing potential.
10. Patient has signed informed consent and is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of hypersensitivity to any drugs or metabolites of PI3K inhibitors or any of the excipients of alpelisib
2. Severe infection requiring intravenous antibiotics within 4 weeks prior to enrolment
3. Patient has had a major surgical procedure within 4 weeks prior to enrolment
4. Prior use of an alpha-specific PI3K inhibitor
5. History of pneumonitis or interstitial lung disease
6. 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
7. Established diagnosis of type I diabetes mellitus, type II diabetes mellitus requiring anti-hyperglycaemic medication or any participant with HbA1c > 6.4%
8. Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes
9. 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
10. History of acute pancreatitis within 1 year of screening or past history of chronic pancreatitis
11. Patient with Child Pugh score B or C
12. Unresolved osteonecrosis of the jaw
13. Impairment of GI function or GI disease that may significantly alter the absorption of the study drug based on investigator discretion
14. Known history of Human Immunodeficiency Virus (HIV) infection (testing for HIV is not mandatory in screening)
15. Known history of severe cutaneous reactions like Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Erythema Multiforme (EM), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
16. Known history of clinically significant, uncontrolled heart disease and/or recent cardiac events including:

* History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis, or myocardial infarction within 6 months prior to the start of study treatment;
* History of documented congestive heart failure (New York Heart Association functional classification III-IV);
* History of impaired Left Ventricular Ejection Fraction (LVEF) < 50% (an assessment of LVEF is not mandatory in screening)
* History of clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place);
* Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) = 160 mmHg and/or Diastolic Blood Pressure (DBP) = 100 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;
* Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or corrected QT interval > 470 msec at screening (using Fridericia correction);
* Bradycardia (heart rate < 50 beats per minute at rest), by electrocardiogram (ECG) or pulse
17. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgement, contraindicate administration of alpelisib (eg. active or uncontrolled severe infection, chronic active hepatitis, immune-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure)
18. Patient is unable to understand and comply with treatment instructions and requirements

MODULE 2

Inclusion Criteria:

1. Adult or paediatric patient, 2 years of age or over where Body Surface Area (BSA) is greater than or equal to 0.4m2.
2. Patient has a clinical diagnosis of a fast-flow vascular malformation
3. 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 mirdametinib
4. A documented genetic alteration in the RAS-MEK-ERK signalling pathway identified by genetic sequencing prior to enrolment in this study
5. 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)
6. Patient has a life expectancy = 12 weeks
7. Participant has the ability to swallow capsules whole if the capsule dosage form is being utilized. This criterion does not apply if participant is utilizing the dispersible tablet form of study treatment
8. 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) = 2 x upper limit of normal (ULN); Total bilirubin < 1.5x ULN (isolated bilirubin > 1.5x ULN is acceptable if bilirubin is fractioned and direct bilirubin < 35%), except where impaired hepatic function is a consequence of the fast-flow malformation and hence is an indication for treatment, in which case impaired hepatic function is acceptable.
* 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; Phosphate = 1x ULN.
9. Patient agrees to abstinence or highly effective contraceptive measures if of childbearing potential (WOCBP)

* Males who are sexually active must use a condom during intercourse while taking mirdametinib and for at least 90 days after stopping mirdametinib and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid. In addition, male participants must not donate sperm during the study and for at least 90 days after stopping mirdametinib
* Females who are of child-bearing potential, defined as all individuals physiologically capable of becoming pregnant, must use a highly effective method of contraception during study treatment and for at least 180 days after the last dose of any study treatment. Highly effective contraceptive methods include:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject) Periodic abstinence (eg., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
* Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the women has been confirmed by follow up hormone level assessment;
* Male partner sterilisation (at least 6 months prior to screening) of the sole partner of a female participant on the study;
* Use of oral (estrogen and progesterone), injected or implanted combined hormonal method of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormonal vaginal ring or transdermal hormone contraception. In the case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
* Women are considered postmenopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhoea with an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of childbearing potential.
10. Patient has signed informed consent and is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations



1. History of hypersensitivity to any drugs or metabolites of MEK inhibitors or any of the excipients of mirdametinib
2. Severe infection requiring intravenous antibiotics within 4 weeks prior to enrolment
3. Patient has had a major surgical procedure within 4 weeks prior to enrolment
4. Prior use of a MEK inhibitor
5. Patient has abnormal QT interval corrected by Fridericia's formula (> 450 msec for male participants, > 470 msec for female participants, or > 480 msec for participants with bundle branch block) (triplicate ECG readings taken approximately 2 to 3 minutes apart and averaged) at Screening;
6. Patient is pregnant or lactating at the time of study registration. A pregnancy test is mandated for persons of child-bearing potential in the screening period
7. Impairment of GI function or GI disease that may significantly alter the absorption of the study drug based on investigator discretion
8. Any clinically significant active or known history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
9. Lymphoma, leukaemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years;
10. Breast cancer within the past 5 years;
11. Known history of Human Immunodeficiency Virus (HIV) infection (testing for HIV is not mandatory in screening)
12. Known history of severe cutaneous reactions like Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Erythema Multiforme (EM), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
13. Patient has a history of, or evidence of, retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration. Patients will be excluded from study participation if they have any of the following risk factors for RVO at Screening:

* Intraocular pressure > 21 mmHg;
* Serum cholesterol > 7.8 mmol/L;
* Serum triglycerides > 3.4 mmol/L;
* Hyperglycaemia (fasting blood glucose > 7.0 mol/L );
* Age specific hypertension

* Patients = 13 years of age with a blood pressure = 140/90 mmHg
* Patients = 12 years of age with a blood pressure = 95th percentile for age + 12 mmHg
14. Known history of glaucoma
15. Known history of clinically significant, uncontrolled heart disease and/or recent (within 6 months [24 weeks] of signing informed consent/assent) cardiac events including:

* History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis, or myocardial infarction within 6 months prior to the start of study treatment;
* History of documented congestive heart failure (New York Heart Association functional classification III-IV);
* History of clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place);
* Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) = 140 mmHg and/or Diastolic Blood Pressure (DBP) = 90 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;
* Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or corrected QT interval > 470 msec at screening (using Fridericia correction);
* Bradycardia (heart rate < 50 beats per minute at rest), by electrocardiogram (ECG) or pulse
16. Patient has recorded a left ventricular ejection fraction (LVEF) < 55% at Screening
17. Patient has experienced a cerebrovascular accident, transient ischaemic attach, or symptomatic pulmonary embolism within 6 months (24 weeks) of signing informed consent/assent.
18. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgement, contraindicate administration of mirdametinib (eg. active or uncontrolled severe infection, chronic active hepatitis, immune-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure)
19. Patient is unable to understand and comply with treatment instructions and requirements

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Parkville
Recruitment hospital [2] 0 0
The Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Peter MacCallum Cancer Centre, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Royal Children's Hospital
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05983159
Trial related presentations / publications
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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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. Erratum In: Nature. 2019 Apr;568(7752):E6. doi: 10.1038/s41586-019-1109-3.
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.
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. Erratum In: J Clin Invest. 2018 Nov 1;128(11):5185. doi: 10.1172/JCI124649.
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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.
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Public notes

Contacts
Principal investigator
Name 0 0
Tony Penington, MBBS, FRACS.
Address 0 0
Study Principal Investigator
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michelle de Silva, PhD
Address 0 0
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Phone 0 0
+61399366109
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Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05983159