Study of Safety and Efficacy of BYL719 With Everolimus or BYL719 With Everolimus and Exemestane in Advanced Breast Cancer Patients, Renal Cell Cancer and Pancreatic Tumors
Conditions
Neoplasms, - Breast Neoplasms, - Kidney Neoplasms, - Pancreatic Neuroendocine Neoplasms
Conditions: official terms
Adenoma, Islet Cell - Apudoma - Breast Neoplasms - Carcinoid Tumor - Carcinoma, Renal Cell - Kidney Neoplasms - Neoplasms - Neuroendocrine Tumors
Conditions: Keywords
Solid tumors,, renal cell carcinoma,, pancreatic neuroendocrine tumors, breast cancer,, PI3K inhibitor,, BYL719,, Everolimus,, Exemestane
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: BYL719 Type: Drug
Name: Everolimus Type: Drug
Name: Exemestane Type: Drug
Overall Status
Recruiting
Summary
Dose escalation part: to determine the highest dose of BYL719 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 BYL719 and Everolimus or BYL719, Everolimus and Exemestane combinations. To explore preliminary signs of efficacy of BYL719 and everolimus, and of the triplet combination (BYL719, everolimus, and exemestane) in selected patient populations by cohort
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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 BYL719+ Everolimus+Exemestane combination - escalation and expansion phases, breast cancer cohort

- 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

Inclusion Criteria for the BYL719+ Everolimus+Exemestane combination - expansion phase, breast cancer cohort previously treated by a mTOR inhibitor

- all of above first 7 criteria plus criteria 12 plus has received a prior mTOR inhibitor treatment as described 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

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

- 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

- 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 BYL719, 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. Patient should also avoid close contact with others who have received live attenuated vaccines

- 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 18 criteria plus have discontinued prior mTOR inhibitor therapy due to non-tolerable toxicity
Locations
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States
Status: Recruiting
Contact: Lori Drummond - 479-872-8130 - ldrummond@hogonc.com
Memorial Sloan Kettering Cancer Center SC - BYL719Z2102
New York, New York, United States
Status: Recruiting
Contact: Nana Akom - 646-888-4425 - akomn@mskcc.org
Novartis Investigative Site
Bordeaux, France
Status: Not yet recruiting
Novartis Investigative Site
Villejuif Cedex, France
Status: Recruiting
Novartis Investigative Site
Hong Kong, Hong Kong
Status: Not yet recruiting
Novartis Investigative Site
Ancona, AN, Italy
Status: Not yet recruiting
Novartis Investigative Site
Milano, MI, Italy
Status: Recruiting
Novartis Investigative Site
Modena, MO, Italy
Status: Not yet recruiting
Novartis Investigative Site
Verona, VR, Italy
Status: Recruiting
Novartis Investigative Site
Amsterdam, Netherlands
Status: Recruiting
Novartis Investigative Site
Utrecht, Netherlands
Status: Not yet recruiting
Novartis Investigative Site
Madrid, Spain
Status: Recruiting
Novartis Investigative Site
Manchester, United Kingdom
Status: Not yet recruiting
Start Date
May 2014
Completion Date
October 2016
Sponsors
Novartis Pharmaceuticals
Source
Novartis
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page