Last Update: Feb 28, 2024
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)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CBYL719F12201
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

This is a prospective Phase II multi-center study with an upfront 16-week, randomized, double-blind, placebo-controlled period, and extension periods, to assess the efficacy, safety and pharmacokinetics of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS).

This study consists of a screening period of up to 42 days, core period of 24 weeks, extension period of 24 weeks and long-term extension period of up to approximately 5 years. The study will enroll adult participants (Group 1), 6-17 years old pediatric participants (Group 2), two exploratory sets of 2-5 years old pediatric participants (Group 3 treated with granules and Group 4 treated with film-coated tablets (FCT)) ) and an exploratory group of 6 to 17 years old pediatric participants (Group 5; treated with FCT [at a higher starting dose than Group 2]).

Eligible participants aged ≥6 years old will be randomized in a 2:1 ratio to alpelisib or matching placebo. Both age groups (group 1 and group 2) will be enrolled in the study in parallel. In the core period, participants will receive treatment in blinded fashion, with an upfront 16-week placebo-controlled period. After Week 16 those participants who were randomized to receive placebo will be switched to active treatment with alpelisib. Those participants who were randomized to receive alpelisib will continue their active treatment.

Participants in Group 4 will be enrolled before Group 3. Group 5 will be open to enrollment after enrollment of Group 2 has been completed. All participants will receive alpelisib in an open-label setting.

Group 3 will be enrolled later, after the completion of the primary analysis when the efficacy, safety and PK data will be available from the participants in Groups 1 and 2 in addition to the data from Group 4 and 5 as available, in order to select the recommended dose for participants in Group 3.

The planned duration of alpelisib treatment in the study will be up to 5 years after randomization/treatment start for all age groups. Participant may be discontinued from treatment with alpelisib earlier due to unacceptable toxicity, confirmed disease progression, death, and/or any other reason at the discretion of the investigator or the participant.

PIK3CA-related Overgrowth Spectrum (PROS)
Phase 2
Recruiting
189
Apr 19, 2021
Jun 07, 2030
All
2 Years - (Child, Adult, Older Adult)

Interventions

Drug

Alpelisib

Adult participants (group 1) will receive 125 mg of alpelisib oral tablets once daily. Pediatric participants (Group 2: 6 to 17 years old) will receive 50 mg of alpelisib oral tablets once daily. Pediatric participants (Group 4: 2 to 5 years old) will receive 50 mg of alpelisib oral tablets once daily, Pediatric participants (Group 3: 2 to 5 years old) will receive alpelisib granules at dose determined based on the primary analysis for efficacy, safety and PK of alpelisib in Groups 1 and 2 in addition to the data from Group 4 as available. Pediatric participants (Group 5: 6 to 17 years old) will receive 125 mg of alpelisib oral tablets once daily.
Drug

Placebo

Participants will receive matching placebo once daily up to week 16.

Eligibility Criteria

Inclusion Criteria:

Signed informed consent and assent (when applicable) from the patient, parent, legal authorized representative or guardian prior to any study related screening procedures are performed
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
Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories

A tissue sample (fresh or archival) is 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.

For China only: Tissue sample collection and biomarker assessments are not applicable.

For Germany only: If archival tissue is available, it must be sent to a Novartis designated central laboratory. If no archival tissue is available, obtaining a fresh tissue biopsy is recommended, if it is not clinically contraindicated, but is not mandatory.

Karnofsky (in patients > 16 years old at study entry)/Lansky (≤16 yrs of age at study entry) performance status index ≥50
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)
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 (Magnetic resonance imaging), and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization.

Exclusion Criteria:

Participant with only isolated macrodactyly, skin 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
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)
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.
Debulking or other major surgery performed within 3 months at time of informed consent
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. Note: Participants receiving anticoagulants for PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study
Participants in Groups 1, 2 ad 5 with documented pneumonitis or interstitial lung disease at time of informed consent and with impaired lung function (e.g., FEV1 or DLCO ≤ 70% of predicted) that is not related to PROS. Participants in Groups 3 and 4 with documented or suspicious pneumonitis or interstitial lung disease based on MRI images at time of informed consent
History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent
Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent
Known history of seizure, or epilepsy, regardless of relatedness to PROS spectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepileptic drug(s) at time of informed consent.
Participants with clinically significant worsening of PROS-related laboratory anomalies, physical signs and symptoms (such as, but not limited to increase of D-dimers, worsening of underlying pain, newly occurring swelling or redness) indicating an uncontrolled condition during the screening phase, particularly if systemic treatment with any other inhibitor of the PI3K/AKT/mTOR pathway was stopped prior to the start of study treatment. This includes but is not limited to hypercoagulability state in participants not receiving prophylactic treatment.

Other inclusion/exclusion criteria may apply

Study Location

Novartis Investigative Site

Recruiting

Montreal,Quebec,H2W 1T8,Canada

Novartis Investigative Site

Recruiting

Montreal,Quebec,H3T 1C5,Canada

Novartis Investigative Site

Recruiting

Toronto,Ontario,M5G 1X8,Canada

Novartis Investigative Site

Recruiting

Shanghai,200011,China

Novartis Investigative Site

Recruiting

Tours 9,37044,France

Novartis Investigative Site

Recruiting

Bordeaux Cedex,33076,France

Novartis Investigative Site

Recruiting

Paris 15,75015,France

Novartis Investigative Site

Recruiting

Dijon,21000,France

Novartis Investigative Site

Recruiting

Duesseldorf,40225,Germany

Novartis Investigative Site

Recruiting

Freiburg,79106,Germany

Novartis Investigative Site

Recruiting

Hamburg,22149,Germany

Novartis Investigative Site

Recruiting

Heidelberg,69120,Germany

Novartis Investigative Site

Recruiting

Leipzig,04103,Germany

Novartis Investigative Site

Recruiting

Pokfulam,Hong Kong

Novartis Investigative Site

Recruiting

Roma,RM,00165,Italy

Novartis Investigative Site

Recruiting

Torino,TO,10126,Italy

Novartis Investigative Site

Recruiting

Nijmegen,6525EX,Netherlands

Novartis Investigative Site

Recruiting

Esplugues De Llobregat,Barcelona,08950,Spain

Novartis Investigative Site

Recruiting

Madrid,28046,Spain

Novartis Investigative Site

Recruiting

Bern,3010,Switzerland

Novartis Investigative Site

Recruiting

Zuerich,CH - 8032,Switzerland

Novartis Investigative Site

Recruiting

Manchester,M13 9WL,United Kingdom

Novartis Investigative Site

Recruiting

West Midlands,Birmingham,B4 6NH,United Kingdom

Washington Univ School of Medicine .

Recruiting

Saint Louis,Yvette Schulz email: [email protected] -- Bryan Sisk,63110 - Missouri,United States

Childrens Hospital Colorado .

Recruiting

Aurora,(720-777-5379) -- Taizo Nakano,80045 - Colorado,United States

NYU Langone Health .

Recruiting

New York,Anna Yaffe (212-263-5940) email: [email protected] -- Francine Blei,10016 - New York,United States

CHOP Abramson Pediatric Resch Ctr

Recruiting

Philadelphia,Tyson Echols email: [email protected] -- Denise Adams,19104 - Pennsylvania,United States

UCSF Birthmarks and Vascular Center

Recruiting

San Francisco,Kathy Nguyen (415-353-7823) email: [email protected] -- Beth Apsel Winger,94158 - California,United States

Cincinnati Children s Hospital Medical Center

Recruiting

Cincinnati,Cincinnati HVMC Research Staff (513-803-4862) email: [email protected] -- Adrienne Hammill,45229-3039 - Ohio,United States

UNC Chapel Hill

Recruiting

Chapel Hill,Miriam Davis (919-966-0985) email: [email protected] -- Julie Blatt,27599 - North Carolina,United States

University of California Los Angeles

Recruiting

Los Angeles,Vivian Y Chang,90095 - California,United States

University of Texas Southwestern Medical Center .

Recruiting

Dallas,Rachel Nam (214-456-5413) email: [email protected] -- Kathleen Ludwig,75235 - Texas,United States

Baylor College Of Medicine

Recruiting

Houston,Cara-Lee Fontaine (713-798-3701) email: [email protected] -- Ionela Iacobas,77030 - Texas,United States

University of Wisconsin Hospital

Recruiting

Madison,Debra Ott (608-890-8070) email: [email protected] -- Beth Drolet,53792 - Wisconsin,United States

Children's Hospital and Regional Medical Center

Recruiting

Seattle,Dhanashree Sawant (206-526-2100) email: [email protected] -- Jonathan A Perkins,98105 - Washington,United States

Worldwide Contacts

If the location of your choosing does not feature any contact detail, please reach out using the information below.

Novartis Pharmaceuticals

Novartis Pharmaceuticals