Breast Neoplasms (Including Advanced or Metastatic Breast Cancer With PIK3CA Mutation), PIK3CA-Related Overgrowth Spectrum (PROS)
Conditions
Keywords
Alpelisib (BYL719), PI3K inhibitor, PIK3CA mutation, Post-trial access, Roll-over study, Long-term safety, Open-label, Continued treatment access, Solid tumors, Breast cancer, PROS
Brief summary
The purpose of this study is to provide post-trial access to alpelisib and to assess its long-term safety when administered as a single agent or in combination with other drugs. This study is intended for participants who are currently receiving alpelisib in a Novartis-sponsored clinical trial (parent study) and, in the Investigator's judgment, would benefit from continued treatment with alpelisib.
Detailed description
Eligible participants are those who are receiving alpelisib, either as a single agent or in combination with other drugs, at the end of one of the following parent studies: CBYL719F12401 (NCT04980833), CBYL719G12301 (NCT04208178), CBYL719C2303 (NCT05038735), CBYL719C1201 (NCT04524000), CBYL719C2201 (NCT04544189), or CLEE011X2107 (NCT01872260). Participants transition directly from the parent study into this roll-over study without a separate screening period. At enrollment, participants continue treatment with the same combination and the same dose that were administered at the end of the parent study. Study visits, treatment administration, and safety assessments generally follow the schedules used in the parent study. Participants continue receiving alpelisib until clinical benefit is no longer observed, study treatment is discontinued for safety or other protocol-defined reasons, or another discontinuation criterion is met. Clinical benefit is evaluated by the investigator at scheduled visits. Safety is monitored throughout the study through the collection of adverse events and serious adverse events. Safety assessments are conducted at regular intervals during treatment in accordance with the study protocol and local clinical practice. At discontinuation of study treatment, participants complete an end-of-treatment visit. All participants are followed for safety for 30 days after the last dose of alpelisib.
Interventions
DRUGAlpelisib
Administered as oral tablets at dose levels as per the parent study, taken once daily.
DRUGFulvestrant
Administered as an intramuscular injection at dose levels and dosing schedule as per standard of care, in accordance with the parent study.
DRUGTrastuzumab
Administered as an intravenous infusion of a reconstituted lyophilized powder at dose levels as per the parent study, given every 21 days.
DRUGPertuzumab
Administered as an intravenous infusion of a solution concentrate at dose levels as per the parent study, given every 21 days.
DRUGLetrozole
Administered as oral tablets at a dose of 2.5 mg, taken once daily, as per the parent study.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Written informed consent/assent, according to local guidelines, signed by the participants and/or by the parents or legal guardian prior to enrolling in the roll-over study. * Participant currently enrolled in a Novartis-sponsored study, is currently receiving alpelisib as a single agent or in combination with other drugs, and has fulfilled all on-treatment requirements in the parent study. * Participant is currently benefiting from the treatment with alpelisib as determined by the Investigator in the parent study. * Participant demonstrated compliance with the visit schedule in the parent study, and in the opinion of the Investigator has shown willingness and ability to comply with future visit schedules, treatment plans, and any other study procedures in this protocol. Key
Exclusion criteria
* Participant had permanently discontinued from alpelisib in the parent study for any reason including withdrawal of consent. * Participant currently has ongoing/unresolved treatment related Grade 3 or higher AEs, and/or any ongoing/unresolved AE or toxicities for which alpelisib dosing has been interrupted in the parent study. Participants meeting all other eligibility criteria may be enrolled once toxicities have improved to allow alpelisib dosing to resume as stated in the parent protocol. * Participant's ongoing treatment is currently approved and reimbursed for their indication at their country level. In exceptional cases where the treatment is reimbursed at the country level, but not individual level, please contact the Novartis Study Team. * Concurrent participation in any other investigational clinical trial other than the parent study. * Pregnant or nursing (breastfeeding) women. * Female participants of childbearing potential who do not consent to use a highly effective method of contraception, and male participants who do not consent to use a condom and/or a highly effective method of contraception, including refraining from sperm donation and complying with measures to prevent exposure of a partner to alpelisib via seminal fluid, for the duration of the study and for one week following discontinuation of alpelisib (or longer if required per parent protocol). Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 53 months | Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with Clinical Benefit Rate (CBR) | Up to approximately 54 months | Clinical benefit is defined as the investigator's assessment that the participant continues to derive benefit from alpelisib treatment, based on overall clinical evaluation at scheduled visits, and that continued treatment is appropriate. |
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed