Managed Access Program (MAP) to Provide Access to Alpelisib (BYL719) for Patients With PIK3CA-Related Overgrowth Spectrum (PROS)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Available

CT.gov ID

NCT04085653

Collaborator

(none)

118

Locations

Study Details

Study Description

Brief Summary

The purpose of this Cohort Treatment Plan is to allow access to alpelisib for patients diagnosed with PIK3CA-Related Overgrowth Spectrum (PROS) who fulfill certain eligibility criteria as specified in this document. The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations

Condition or Disease	Intervention/Treatment	Phase
PIK3CA-Related Overgrowth Spectrum (PROS)	Drug: alpelisib

Study Design

Study Type:

Expanded Access

Official Title:

Managed Access Program (MAP) to Provide Access to Alpelisib (BYL719) for Patients With PIK3CA-Related Overgrowth Spectrum (PROS)

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Patients eligible for inclusion in this Treatment Plan have to meet all of the following criteria:

Adult or pediatric patients ≥ 2 years of age, with a diagnosis of PROS preferably with evidence of a mutation in the PIK3CA gene
The treating physician has determined that the patient's condition is severe or life threatening, treatment is necessary and there are no other feasible alternatives for the patient.
Confirmed adequate bone marrow function Written patient informed consent must be obtained prior to start of treatment

Exclusion criteria

Patients eligible for this Treatment Plan must not meet any of the following criteria:

Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib.
Patient with uncontrolled diabetes mellitus type I or not controlled type II (based on FPG and HbA1c, see inclusion criterion 2)
Patient who has other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgment, contraindicate administration of alpelisib (eg. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
Patient has a known history of Severe Cutaneous Adverse Reactions (SCAR) like Steven Johnson's syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
History of pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
Subject with Child Pugh score B or C
Subjects with unresolved osteonecrosis of the jaw
Subject is currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment:

Strong inducers of CYP3A4
Inhibitors of BCRP

Patient has a known history of Human Immunodeficiency Virus (HIV) infection (testing not mandatory unless required by local regulations or requirements).
Patient who is concurrently being treated with drugs known to be strong inhibitors or inducers of the isoenzyme CYP3A; switching to different medications prior to start of program treatment is allowed within the last 5 days prior to starting program treatment
Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to start of program treatment, or who have not fully recovered from side effects of such treatment.

Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).

Male patient who does not apply highly effective contraception during the treatment with alpelisib and through the duration as defined below after the final dose of alpelisib. Sexually active males should use a condom during intercourse while taking drug 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 vasectomized men in order to prevent delivery of the drug via seminal fluid
Subject is not able to understand and to comply with treatment instructions and requirements
Subject is a nursing (lactating) or pregnant woman as confirmed by a positive serum (hCG) test prior to initiating study treatment
Subject is a woman of child-bearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and at least for 1 week after the last dose of any study treatment.

Highly effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the subject ). Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (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 woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject
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 case of use or oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

Note: Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea 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 not of child bearing potential.

Subject is a sexually active male unwilling to use a condom during intercourse while taking study treatment, and for 1 week after stopping alpelisib. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm during study and up to the time period specified above.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Arkansas Childrens Hospital Dept. Pediatric/Div Hem/Onc	Little Rock	Arkansas	United States	72202
3	Children's Hospital Los Angeles Childen's Center for Cancer	Los Angeles	California	United States	90027
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
5	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
6	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
7	UCLA Medical Center	Los Angeles	California	United States	90095
8	University of California at Los Angeles	Los Angeles	California	United States	90095
9	Stanford University Medical Center Div. of Pediatric Rheumatology	Palo Alto	California	United States	94304-1509
10	Lucile Packard Children s Hospital Stanford University	Palo Alto	California	United States	94304
11	Children's Specialists of San Diego Medical Group	San Diego	California	United States	92123
12	Rady Children s Hospital Dept of Oncology	San Diego	California	United States	92123
13	Rady Children s Hospital Sickle Cell Disease Center	San Diego	California	United States	92123
14	Rady Childrens Hospital	San Diego	California	United States	92123
15	AI Dupont Children Hospital	Wilmington	Delaware	United States	19803
16	Alfred I DuPont Hospital for Children	Wilmington	Delaware	United States	19899
17	Children's National Med Center StudyCoord:ACZ886G2301/01E1/05	Washington	District of Columbia	United States	20010
18	Childrens National Hospital Ctr - Cancer & Blood Disorders	Washington	District of Columbia	United States	20010
19	Childrens National Hospital	Washington	District of Columbia	United States	20010
20	Nicklaus Childrens Hospital	Miami	Florida	United States	33155
21	Children s Healthcare of Atlanta Aflac Blood Cancer Center	Atlanta	Georgia	United States	30322
22	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
23	University of Iowa Health Care Dept of Pediatrics & Pulmonary	Iowa City	Iowa	United States	52242
24	Boston Childrens Hospital Pediatric Heamatology Oncology	Boston	Massachusetts	United States	02215
25	Children's Hospital and Clinics of Minnesota Childrens Hosp/Clinic	Minneapolis	Minnesota	United States	55404
26	Atlantic Medical Group	Morristown	New Jersey	United States	07960
27	Roswell Park Cancer Institute Pediatrics	Buffalo	New York	United States	14263
28	Cohen Children's Medical Center of New York Oncology	New Hyde Park	New York	United States	11040
29	NYU Langone Health	New York	New York	United States	10016
30	NYU Laura and Isaac Perlmutter Cancer Center	New York	New York	United States	10016
31	Mission Hospital	Asheville	North Carolina	United States	28801
32	Cincinnati Children's Hospital Medical Center Cancer & Blood Disease Inst.	Cincinnati	Ohio	United States	45229-3039
33	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
34	Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
35	Oklahoma State University Health Sciences Center Pediatric Hem/Onc	Oklahoma City	Oklahoma	United States	73104
36	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
37	Doernbecher Children's Hospital	Portland	Oregon	United States	97239
38	Children's Hospital of Philadelphia Pediatric Oncology Clinic	Philadelphia	Pennsylvania	United States	19104
39	The Childrens Hospital of Philadelphia Children's Hosp Philadelphia	Philadelphia	Pennsylvania	United States	19104
40	The Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
41	LeBonheur Children's Medical Center	Memphis	Tennessee	United States	38103
42	Monroe Carell Jr Childrens Hospital at Vanderbilt	Nashville	Tennessee	United States	37232
43	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
44	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
45	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
46	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
47	Dell Childrens Medical Center of Central Texas	Austin	Texas	United States	78723
48	Texas Cancer Center ( Medical City Dallas Hospital)	Dallas	Texas	United States	75230
49	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235-8858
50	University of Texas Southwestern Medical Center UT Southwestern	Dallas	Texas	United States	75390-8852
51	University of Texas Southwestern Medical Center Regulatory	Dallas	Texas	United States	75390
52	UT Southwestern Medical Center Pediatric Hematology/Onc	Dallas	Texas	United States	75390
53	Texas Childrens Hospital CFTY720D2311	Houston	Texas	United States	77030
54	Texas Childrens Hospital Oncology Department	Houston	Texas	United States	77030
55	Texas Childrens Hospital	Houston	Texas	United States	77030
56	The University of Vermont Medical Center	Burlington	Vermont	United States	05401
57	UVA Children s Hospital	Charlottesville	Virginia	United States	22903
58	Children's Hospital of Richmond at VCU Pediatric Hematology Oncology	Richmond	Virginia	United States	23219
59	Children's Hospital of Richmond at VCU	Richmond	Virginia	United States	23219
60	Virginia Mason Medical Center Buck 2	Seattle	Washington	United States	98101
61	Virginia Mason Medical Center	Seattle	Washington	United States	98101
62	Children's Hospital and Regional Medical Center	Seattle	Washington	United States	98105-0371
63	Children's Hospital and Regional Medical Center	Seattle	Washington	United States	98105
64	Seattle Childrens Hospital	Seattle	Washington	United States	98105
65	Childrens Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
66	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
67	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
68	Novartis Investigative Site	Capital Federal	Buenos Aires	Argentina	C1425EFD
69	Novartis Investigative Site	Randwick	New South Wales	Australia	2031
70	Novartis Investigative Site	Parkville	Victoria	Australia	3052
71	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
72	Novartis Investigative Site	Brussel		Belgium	1200
73	Novartis Investigative Site	Gent		Belgium	9000
74	Novartis Investigative Site	Gilly		Belgium	6060
75	Novartis Investigative Site	Haine-saint-Paul		Belgium	7100
76	Novartis Investigative Site	Leuven		Belgium	3000
77	Novartis Investigative Site	Winnipeg	Manitoba	Canada	R3E 0V9
78	Novartis Investigative Site	Kitchener	Ontario	Canada	N2G 1G3
79	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 1X8
80	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N0L6
81	Novartis Investigative Site	Montreal		Canada
82	Novartis Investigative Site	Quebec		Canada	G1R 2J6
83	Novartis Investigative Site	Quebec		Canada	H3T IC5
84	Novartis Investigative Site	Quebec		Canada
85	Novartis Investigative Site	Vancouver		Canada	V7L 2L7
86	Novartis Investigative Site	Zagreb		Croatia	10000
87	Novartis Investigative Site	Aarhus		Denmark	8000
88	Novartis Investigative Site	Copenhagen		Denmark	DK-2100
89	Novartis Investigative Site	Helsinki		Finland	00290
90	Novartis Investigative Site	Helsinki		Finland	9
91	Novartis Investigative Site	Munich	Bavaria	Germany
92	Novartis Investigative Site	Athens	GR	Greece	151 23
93	Novartis Investigative Site	Mumbai	Maharashtra	India	400 053
94	Novartis Investigative Site	Dublin 4		Ireland	4
95	Novartis Investigative Site	Dublin		Ireland	12
96	Novartis Investigative Site	Ramat Gan		Israel	52621
97	Novartis Investigative Site	Seoul		Korea, Republic of	138 736
98	Novartis Investigative Site	Kuala Lumpur		Malaysia	59100
99	Novartis Investigative Site	Durango		Mexico	34000
100	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
101	Novartis Investigative Site	Nijmegen		Netherlands	6500 MB
102	Novartis Investigative Site	Nijmegen		Netherlands	6525EX
103	Novartis Investigative Site	Warszawa		Poland	04-730
104	Novartis Investigative Site	Moscow		Russian Federation	115478
105	Novartis Investigative Site	Moscow		Russian Federation	117198
106	Novartis Investigative Site	Singapore		Singapore	229899
107	Novartis Investigative Site	Ljubljana		Slovenia	1000
108	Novartis Investigative Site	Oviedo	Asturias	Spain	33011
109	Novartis Investigative Site	Esplugues de Llobregat	Barcelona	Spain	08950
110	Novartis Investigative Site	Barcelona	Cataluna	Spain	08950
111	Novartis Investigative Site	Terrassa	Catalunya	Spain	08221
112	Novartis Investigative Site	Madrid		Spain	28041
113	Novartis Investigative Site	Madrid		Spain	28046
114	Novartis Investigative Site	Lund		Sweden	22185
115	Novartis Investigative Site	Zuerich		Switzerland	CH - 8032
116	Novartis Investigative Site	Kaohsiung City		Taiwan	807
117	Novartis Investigative Site	Taipei		Taiwan	11217
118	Novartis Investigative Site	Abu Dhabi		United Arab Emirates	51900