EPIK-P2: A Phase II double-blind study with an upfront, 16-week randomized, placebo-controlled period, to assess the efficacy, safety and pharmacokinetics of alpelisib (BYL719) in pediatric and adult patients with PIK3CA-related overgrowth spectrum (PROS)
- Conditions
- PIK3CA-related overgrowth100276561004704310040795
- Registration Number
- NL-OMON54117
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 14
1. Patients with diagnosis of PROS with symptomatic and /or progressive
overgrowth and at least one measurable PROS-related lesion confirmed by blinded
independent review committee (BIRC) assessment
2. Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in
local laboratories
3. A tissue sample (fresh or archival) must be available to be sent to a
Novartis-designated central laboratory. If archival tissue is not available,
collection of a fresh tissue biopsy is required for participants in Groups 1, 2
and 5, if it is not clinically contraindicated. For participants in Groups 3
and 4, a fresh tissue biopsy is not mandatory.
4. Karnofsky (in patients > 16 years old at study entry)/Lansky (<=16 yrs of age
at study entry) performance status index >=50
5. Adequate bone marrow and organ function including Fasting plasma glucose
(FPG) <= 140 mg/dL (7.7 mmol/L)* and Glycosylated hemoglobin (HbA1c) <= 6.5%
(both criteria have to be met) (as assessed by central laboratory for
eligibility within.
6. Presence of at least one PROS-related measurable lesion defined as a lesion
with longest diameter >=2 cm, when the volume can be accurately and reproducibly
measured by MRI, and associated with complaints, clinical symptoms or
functional limitations affecting the patient's everyday life. Measurability
must be confirmed by BIRC before randomization.
For the full inclusion criteria, please refer to Section 5.1. of protocol
1. Participant with only isolated macrodactyly, epidermal nevus/nevi and
macroencephaly (the only clinical feature or a combination of any of three of
them), in absence of other PROS-related lesions at the time of informed consent.
2. Previous treatment with alpelisib and/or any other PI3K inhibitor(s) (except
treatment attempt, defined as the attempt to treat PROS with any of PI3K
inhibitors, with treatment duration less than 2 weeks and stopped at least 4
weeks prior to the first dose of study medication with alpelisib)
3. Radiation exposure for PROS treatment purpose within the previous 12 months
on those PROS areas which are expected to qualify for target lesions (except
lesion(s) progressing after completion of radiotherapy) at time of informed
consent.
4. Debulking or other major surgery performed within 3 months at time of
informed consent.
5. Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per
CTCAE v.4.03) within 30 days before informed consent, and/or
sclerotherapy/embolization for vascular complications performed within 6 weeks
before informed consent. Participants (receiving anticoagulants for
PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may
be included in the study).
6. Participants with documented pneumonitis or interstitial lung disease at
time of informed consent.
7. History of acute pancreatitis within 1 year before informed consent or past
medical history of chronic pancreatitis at time of informed consent.
8. Participants with an established diagnosis of type I diabetes mellitus or
uncontrolled type II diabetes mellitus at time of informed consent.
9. Known history of seizure, or epilepsy, regardless of relatedness to PROS
sprectrum at time of informed consent, when epilepsy is not controlled and/or
the patient may not be switched to non-enzyme inducing antiepilectic drug(s) at
time of informed consent.
10. Participants with clinically significant worsening of the PROS-related
signs and symptoms (e.g. increase of D-dimers, worsening of underlying
pain, newly occurring swelling or redness) indicating an uncontrolled
condition during screening phase, particularly if systemic treatment with
any other inhibitor of the PI3K/AKT/mTOR pathway was stopped prior
to the start of the study treatment. This includes but is not limited to
hypercoagulability state in participants not receiving prophylactic
treatment.
For the full inclusion criteria, please refer to Section 5.2 of protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoint for primary objective:<br /><br>Response (yes/no) defined by achieving at least 20% reduction from baseline in<br /><br>the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded<br /><br>independent review committee (BIRC)) at Week 24, provided that none of the<br /><br>individual target lesions has >= 20% increase from baseline<br /><br>and in absence of progression of non-target lesions and without new lesions.<br /><br>Confirmation of response requires a subsequent imaging assessment performed at<br /><br>least 4 weeks after the onset of the response.See Section 2.1 for Primary<br /><br>Estimands and Section 8.3 for response definition.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Endpoint for key secondary objective:<br /><br>Response at week 16 (by BIRC): See Section 2.2 for secondary Estimands and<br /><br>Section 8.3 for response definition.<br /><br><br /><br>To assess the efficacy of alpelisib as measured by the proportion of<br /><br>participants with a response at Week 24 (by BIRC) in Groups 1 and 2<br /><br><br /><br>For endpoints for other and exploratory objectives see also protocol section 2<br /><br>(Objectives, endpoints and estimands</p><br>