Overview

Study of Safety and Efficacy of Alpelisib With Everolimus or Alpelisib With Everolimus and Exemestane in Advanced Breast Cancer Patients, Renal Cell Cancer and Pancreatic Tumors

Status:
Completed
Trial end date:
2019-04-12
Target enrollment:
0
Participant gender:
All
Summary
Dose escalation part: to determine the highest dose of alpelisib administered on a daily basis when given in combination with daily everolimus or in combination with daily everolimus and exemestane. Dose expansion part: To describe safety and tolerability of the alpelisib and everolimus or alpelisib, everolimus and exemestane combinations.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Novartis Pharmaceuticals
Treatments:
Everolimus
Exemestane
Sirolimus
Criteria
Inclusion Criteria For entire trial:

- Adult > or = 18 years old

- has signed the Informed Consent Form

- has tumor tissue available for the analysis as described in the protocol

- has an Eastern Cooperative Oncology Group performance status ≤2

- has adequate bone marrow and organ function as defined in the protocol

- is able to swallow and retain oral medication

- has either measurable or non-measurable disease as per RECIST 1.1.

Inclusion Criteria for the BYL719+ Everolimus combination - escalation phase - all above
plus has a histologically/cytologically confirmed metastatic and/or recurrent solid tumors
for whom no standard therapy exists.

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, renal cell
carcinoma cohort - all of above first 7 criteria plus has an histologically/cytologically
confirmed Renal Cell Cancer as detailed in the protocol

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, pancreatic
NeuroEndocrine Tumor cohort

- all of above first 7 criteria plus has an histologically/cytologically confirmed
pancreatic NeuroEndocrine Tumor as detailed in the protocol

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, mTOR
inhibitor-pretreated patients' cohort - all of above first 7 criteria plus has a
histologically and/or cytologically confirmed solid malignancy as described in the protocol

Inclusion Criteria for the breast cancer cohorts in escalation and expansion phases, - all
of above first 7 criteria plus is post-menopausal and has a histologically and/or
cytologically confirmed diagnosis of breast cancer as described in the protocol

Specific Inclusion Criteria at the time of cross-over (breast cancer, expansion phase),

- Patient randomized to the alpelisib and exemestane combination who has a radiologically
documented progressive disease as detailed in the protocol

Exclusion Criteria:

- Patient has received previous treatment with a PI3K and/or AKT and/or mTOR inhibitor
(mTOR inhibitor is allowed in expansion cohorts where patients should have areceived a
prior mTOR inhibitor)

- Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs

- Patient with primary central nervous system (CNS) tumor or CNS tumor involvement as
detailed in the protocol

- Patient with diabetes mellitus, or documented steroid-induced diabetes mellitus

- Patient has a history of another malignancy within 2 years prior to starting study
treatment as described in the protocol

- Patient who has not recovered to grade 1 or better (except alopecia) from related side
effects of any prior antineoplastic therapy as detailed in the protocol

- Patient who has had systemic therapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to starting study treatment

- Patient who has received radiotherapy ≤ 4 weeks prior to starting study drugs, with
exception of palliative radiotherapy (≤ 2 weeks prior to starting study drugs), who
has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or
from whom ≥ 30% of the bone marrow was irradiated

- Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or
who has not recovered from side effects of such procedure

- Patient has a clinically significant cardiac disease or impaired cardiac function or
any severe and/or uncontrolled medical conditions as detailed in the protocol

- Patient who is currently receiving medication with a known risk of prolonging the QT
interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be
discontinued or switched to a different medication prior to starting study drug
treatment

- Patient who has participated in a prior investigational study within 30 days prior to
enrollment as described in the protocol

- Patient who is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzymes CYP34A or CYP2C8 as described in the protocol.
Switching to a different medication prior to start of treatment is allowed

- Patient with impaired gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral alpelisib, everolimus, exemestane

- Patient with known positive serology for human immunodeficiency virus

- Patients who have received live attenuated vaccines within 1 week of start of study
drug and during the study as specified in the protocol.

- Pregnant or nursing (lactating) woman as detailed in the protocol.

- Patient who does not apply highly effective contraception during the study and through
the duration as defined in the protocol

- Patients in the mTOR inhibitor-pretreated cohorts: all of above first 19 criteria plus
have discontinued prior mTOR inhibitor therapy due to non-tolerable toxicity