VATCH (Vascular Anomaly Analysis for Therapy Choice): Phase II Study of Alpelisib Treatment in Subjects With TIE2/PIK3CA Pathway Driven Vascular Anomalies
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 61
- Locations
- 1
- Primary Endpoint
- Percentage of subjects with a Substantial Response or Intermediate Response to Alpelisib using an Individualized Response Criteria
Overview
Brief Summary
The study will enroll participants 2 months of age up to 30 years of age. The purpose of this study is to assess the effectiveness and safety of Alpelisib (the "Study Drug") in patients with PIK3CA/TIE-2/TEK pathway driven vascular anomalies (VA). Alpelisib has been approved by the U.S. Food and Drug Administration (FDA) for treating adults and children with certain types of breast cancer. Its use in this study is considered experimental because FDA has not approved the study drug for treating people with VAs.
Study participation will last for up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP)'s Philadelphia Campus. Participants will need to take the study drug Alpelisib for at least 2 years, or up to 3 years in total if there is a positive response. Participating in this research means you will attend up to 16 clinic visits for the purposes of the study. Most visits will take approximately 30 minutes, but some visits will take approximately 2 hours, because you will be asked to complete questionnaires about your experience. Participating in this research also means taking the study drug, having pictures taken, and completing study drug diaries. There is also an optional portion to this study that involves collecting blood for biomarker testing.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 30 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent and assent (when applicable)
- •Males or females age ≥ 2 years to \<=30 years at the time of informed consent.
- •Have a documented PIK3CA or somatic TIE2/TEK variant.
- •Have a symptomatic vascular anomaly in need of medical therapy.
- •Have a disease-related lesion or lesions which can be measured
- •Have a Lansky or Karnofsky performance status score of ≥
- •Have acceptable organ function
- •(For persons who can get pregnant) Have a negative serum or urine pregnancy test within 7 days prior to starting study medication.
- •Must agree to the use an acceptable method of contraception
- •Subjects that have received alpelisib previously either via Managed Access Program from Novartis or commercial supply are eligible to enroll IF they have been off alpelisib for at least 7 days and there is clinical progression/worsening while off treatment
Exclusion Criteria
- •Subject with only epidermal nevus/nevi in the absence of other PIK3CA vascular anomaly/overgrowth
- •Debulking or other major surgery performed within 30 days, at time of informed consent
- •Clinically meaningful bleeding related to VA: Grade 2 within 14 days or Grade 3 and more within 28 days before study treatment start as per CTCAE v. 5.0
- •Sclerotherapy/embolization for vascular complications performed within 14 days before informed consent.
- •Prior medications that are not allowable per the study protocol
- •Participation in any other prior investigational study within 4 weeks prior to study treatment start and within 5 half-lives of the investigational product, whichever is longer
- •Supportive care use of anticoagulants and compression garments is allowed. Subjects must have been using these interventions in an unchanged manner for 30 days before study enrollment.
- •History of prior and or ongoing malignancy, or ongoing investigations or treatment for malignancy at time of informed consent.
- •Clinically significant heart disease not due to VA
- •Documented pneumonitis or interstitial lung disease not due to VA
Arms & Interventions
Main Study
This arm will determine the proportion of subjects with an objective beneficial response to alpelisib at the end of cycle 6 using an individualized response criterion based on radiologic assessment, Patient Reported Outcomes (PROs) and Clinical Benefit Assessment (CBA). It will also determine the safety of oral trametinib in children and young adults with PIK3CA/TIE-2/TEK pathway driven vascular anomalies through various laboratory testing and clinical observations.
Intervention: alpelisib (BYL719) (Drug)
Outcomes
Primary Outcomes
Percentage of subjects with a Substantial Response or Intermediate Response to Alpelisib using an Individualized Response Criteria
Time Frame: Individualized Response Criteria will be evaluated after 6 cycles (each cycle is 28 days) and then every 6 months until the end of the study (approximately 1.5 years)
Individualized Response is a composite outcome determined by the combined results of the following 3 distinct study assessments after cycle 6: Radiologic evaluation, PROMIS Patient reported outcome (PRO) measurements, and Clinical Benefit Assessments (CBA). The results of these 3 distinct assessments will be evaluated using a set of specific criteria to determine the Individualized Response to treatment (i.e. "Substantial Response" = Improvement in Radiologic assessment by 20%, AND improvement in Global Health PROs by 3T-score points, AND improvement in at least 1 CBA, AND no clinically meaningful worsening of disease). Each subject will be determined to have: 1) Substantial Response, or 2) Intermediate Response, or 3) Stable disease, or 4) Worsening disease. A subject that is found to have a Substantial Response or Intermediate Response is considered to have a "beneficial response." Statistical analyses will be run to determine the percentage of subjects with a beneficial response.
Relative size of target lesion(s) as determined by radiologic assessment
Time Frame: Measured at screening and after cycles 6, 12, and 24. Each cycle is 28 days.
\*\*For subjects with radiologically evaluable disease only\*\* The target lesion(s) will be measured at screening using imaging modality of choice based on underlying vascular anomaly (e.g. Magnetic Resonance Imaging (MRI), Magnetic Resonance Lymphangiography (MRL), US, X-rays, CT scan). MRI or MRL imaging will be recommended as primary imaging modality. For subjects with disease manifestation better characterized by alternative quantitative imaging modality (e.g. X-ray or ultrasound) this may be substituted and used as alternative imaging. Up to 3 lesions will be identified as target lesions and recorded and measured at screening. The same method of assessment and the same technique will be used to characterize each target lesion at the specified follow-up timepoints. CBA can be substituted for radiologic evaluation in subjects without radiologically evaluable disease.
Quality of life as evaluated by PROMIS Patient Reported Outcome (PRO) questionnaire T-scores
Time Frame: Begin at screening and after cycles 6, 12, and 24. If subject enters extension phase, will continue to measure every 6 cycles until end of therapy (approximately 1 year). Each cycle is 28 days.
Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires will be distributed to subjects and caregivers (if applicable.) A raw score will be calculated for each PROMIS subscale. Raw scores will then be translated into a T-score metric with mean of 50 (standard deviation of 10). A higher T-score means more of the outcome being measured. Global health measures will be used as the primary outcome. Change in quality of life will be evaluated and applied to the Individualized Response Criteria using the PROMIS global health T-scores.
Secondary Outcomes
No secondary outcomes reported