Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04085653




Registration number
NCT04085653
Ethics application status
Date submitted
5/09/2019
Date registered
11/09/2019
Date last updated
13/09/2023

Titles & IDs
Public title
Managed Access Program (MAP) to Provide Access to Alpelisib (BYL719) for Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
Scientific title
Managed Access Program (MAP) Cohort Treatment Plan CBYL719F12001M to Provide Access to Alpelisib (BYL719) for Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
Secondary ID [1] 0 0
CBYL719F12001M
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PIK3CA-Related Overgrowth Spectrum (PROS) 0 0
Condition category
Condition code

Intervention/exposure
Study type
Expanded Access
Description of intervention(s) / exposure
Treatment: Drugs - alpelisib

Treatment: Drugs: alpelisib
Alpelisib will be provided as 50 mg, 125mg and 200 mg film coated tablets as individual patient supply, and will be dosed on a flat scale of mg/day not to be adjusted to body weight or surface area.
In Adult patients, alpelisib will be administered at a starting dose of 250 mg orally once daily on a continuous dosing schedule and can be adjusted for toxicity per the recommendations in this treatment plan.
In Pediatric patients, alpelisib will be administered at a maximum starting dose of 50 mg orally once daily on a continuous dosing schedule and can be interrupted for toxicity per the recommendations in this treatment plan; no dose reductions are allowed.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes

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

1. Adult or pediatric patients with a diagnosis of PROS preferably with evidence of a
mutation in the PIK3CA gene

2. 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.

3. Confirmed adequate bone marrow function Written patient informed consent must be
obtained prior to start of treatment
Minimum age
No limit
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

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

1. Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor
or any of the excipients of alpelisib.

2. Patient with uncontrolled diabetes mellitus type I or not controlled type II (based on
fasting plasma glucose (FPG) and HbA1c)

3. 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.)

4. 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).

5. History of pancreatitis within 1 year of screening or past medical history of chronic
pancreatitis

6. Chronic liver disease patients with Child Pugh score B or C

7. Subjects with unresolved osteonecrosis of the jaw

8. 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

9. Patient has a known history of Human Immunodeficiency Virus (HIV) infection (testing
not mandatory unless required by local regulations or requirements).

10. 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).

11. Male patient who does not use 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 1 week after stopping alpelisib and should not father a child in this period.
In addition, male participants must not donate sperm during study and up to the time
period specified above.

12. Subject or caregiver (in the case of a pediatric subject) is not able to understand
and to comply with treatment instructions and requirements

13. Subject is a nursing (lactating) or pregnant woman as confirmed by a positive serum
(hCG) test prior to initiating study treatment

14. 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 unilateral oophorectomy, 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 and/or confirmed by hormonal status (FSH
and estradiol) or have undergone 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 unilateral oophorectomy, only when the reproductive
status of the woman had been confirmed by hormonal levels (FSH and estradiol), she will be
considered not of child bearing potential

Study design
Purpose of the study
Allocation to intervention
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
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Available
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT04085653
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04085653