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PI3K Inhibitor

Alpelisib for Overgrowth Spectrum (EPIK-P2 Trial)

Phase 2

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus 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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5 years

Summary

This trial is testing a new drug to see if it's effective and safe for kids and adults with a growth disorder.

Who is the study for?

This trial is for pediatric and adult patients with PIK3CA-related Overgrowth Spectrum (PROS) who have at least one measurable lesion over 2 cm confirmed by MRI. Participants must be able to provide a tissue sample, have stable blood sugar levels, and not have had previous treatment with alpelisib or similar drugs. Those with isolated macrodactyly, skin nevus/nevi, macroencephaly without other lesions, recent radiation or surgery in the area of interest are excluded.

What is being tested?

The study tests the effectiveness and safety of Alpelisib compared to a placebo in treating PROS. Initially, there's a 16-week blind phase where neither doctors nor participants know who gets Alpelisib or placebo. After that period, all may receive Alpelisib during extension periods while monitoring how their bodies absorb the drug.

What are the potential side effects?

While specific side effects for this trial aren't listed here, common ones from similar medications include nausea, diarrhea, increased blood sugar levels which could affect diabetes control; rash; fatigue; and potential liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have PROS with worsening symptoms and a confirmed measurable lesion.

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My tests show a PIK3CA gene mutation.

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I am mostly able to care for myself but may need help.

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My blood sugar and HbA1c levels are within the required range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with type I diabetes or my type II diabetes is not under control.

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I have had acute pancreatitis within the last year or have chronic pancreatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of participants randomized to alpelisib with a confirmed objective response by BIRC in Group 1 and Group 2

Secondary study objectives

Change from Baseline in patient-reported pain assessed by Brief Pain Inventory (BPI) Worst Pain intensity item or Wong-Baker Faces Scale (age appropriate) in pediatric and adult populations

Change from baseline to Week 16 in Brief Pain Inventory (BPI) Worst Pain intensity in Group 1 and 2

Change from baseline to Week 16 in Patient Global Impression of Symptom Severity (PGIS) in Group 1 and 2

+19 more

Side effects data

From 2023 Phase 3 trial • 572 Patients • NCT02437318

62%

Hyperglycaemia

57%

Diarrhoea

45%

Nausea

35%

Rash

35%

Decreased appetite

26%

Vomiting

26%

Weight decreased

24%

Fatigue

24%

Stomatitis

20%

Asthenia

20%

Alopecia

18%

Mucosal inflammation

18%

Pruritus

17%

Dysgeusia

17%

Headache

15%

Dry skin

14%

Oedema peripheral

14%

Pyrexia

14%

Back pain

13%

Rash maculo-papular

11%

Dyspepsia

11%

Abdominal pain

11%

Arthralgia

10%

Dry mouth

10%

Urinary tract infection

10%

Blood creatinine increased

10%

Gamma-glutamyltransferase increased

10%

Aspartate aminotransferase increased

10%

Cough

Nasopharyngitis

Pain in extremity

Dizziness

Hypertension

Anaemia

Constipation

Alanine aminotransferase increased

Hypokalaemia

Dyspnoea

Myalgia

Muscle spasms

Insomnia

Lipase increased

Abdominal pain upper

Lymphoedema

Musculoskeletal pain

Erythema

Upper respiratory tract infection

Bone pain

Hot flush

Osteonecrosis of jaw

Acute kidney injury

Pneumonitis

Pulmonary embolism

Dehydration

Upper gastrointestinal haemorrhage

General physical health deterioration

Cellulitis

Pleural effusion

Hypersensitivity

Pneumonia

Hyponatraemia

Muscular weakness

Brain oedema

Renal failure

Erythema multiforme

100%

80%

60%

40%

20%

Study treatment Arm

Placebo qd + Fulvestrant

Alpelisib qd + Fulvestrant

Trial Design

7Treatment groups

Experimental Treatment

Placebo Group

Group I: Pediatric cohort (group 5: 6-17 years old)-Alpelisib FCTExperimental Treatment1 Intervention

Pediatric participants (6 to 17 year old) will receive 125 mg alpelisib film-coated (FCT) once daily, in an open-label setting.

Group II: Pediatric cohort (group 4: 2 to 5 years old)- Alpelisib FCTExperimental Treatment1 Intervention

Pediatric participants (2 to 5 years old) will receive 50 mg of alpelisib film-coated tablets (FCT) once daily in an open-label setting.

Group III: Pediatric cohort (group 3: 2 to 5 years old)- Alpelisib granulesExperimental Treatment1 Intervention

Pediatric participants (2 to 5 years old) will receive alpelisib with the alpelisib granules formulation 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 and 5 as available. An extrapolation approach will be used for dose selection for this group.

Group IV: Pediatric cohort (group 2: 6 to 17 years old) -AlpelisibExperimental Treatment1 Intervention

During double-blind randomized study period (from baseline up to Week 16, pediatric participants (6 to 17 years old) will be randomized to receive alpelisib (50 mg, oral, once daily). After Week 16, participants will continue their active treatment at the same dose level.

Group V: Adult cohort (group 1)- AlpelisibExperimental Treatment1 Intervention

During double-blind randomized study period (from baseline up to Week 16), adult participants will be randomized to receive alpelisib (125 mg, oral, once daily). After Week 16, participants will continue their active treatment at the same dose level.

Group VI: Adult cohort (group 1)- PlaceboPlacebo Group2 Interventions

During double-blind randomized study period (from baseline up to Week 16), adult participants will be randomized to receive placebo (125 mg, oral, once daily). After Week 16, participants will be switched to active treatment with alpelisib at the placebo dose level received at the end of the placebo period.

Group VII: Pediatric cohort (group 2: 6 to 17 years old)-PlaceboPlacebo Group2 Interventions

During double-blind randomized study period (from baseline up to Week 16), pediatric participants (6 to 17 years old) will be randomized to receive Placebo (50mg, oral, once daily). After Week 16, participants will be switched to active treatment with alpelisib at the placebo dose level received at the end of the placebo period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alpelisib

2018

Completed Phase 3

~960

0 / 6Eligibility criteria met