A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

Phase 1

Completed

• Conditions: Estrogen Receptor Positive Breast Cancer; Advanced Solid Tumors With an Alteration of the PIK3CA Gene
• Interventions: Drug: BYL719; Drug: Fulvestrant

• Registration Number: NCT01219699
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-05
• Study First Submitted: 2010-10-06
• Study First Submitted QC: 2010-10-11
• Study First Posted: 2010-10-13
• Primary Completion: 2015-02-05
• Study Completion: 2020-04-16
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-21
• Last Update Posted: 2020-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

Inclusion Criteria

• Patients with histologically-confirmed, advanced unresectable solid tumors who have progressed within three months before screening/baseline visit Only patients who have confirmed PIK3CA status (wild type, mutation or amplification) will be allowed for screening (patients participating in the combination arm must be eligible for treatment with fulvestrant)
• Availability of a representative formalin fixed paraffin embedded tumor tissue sample
• At least one measurable or non-measurable lesion
• Age ≥ 18 years
• World Health Organization (WHO) Performance Status ≤ 2
• Good organ (hepatic, kidney, BM) function at screening/baseline visit

Exclusion Criteria

• Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy (anti-epileptic therapy is allowed).
• Prior treatment with PI3K, AKT or mTOR inhibitor and failure to benefit
• Patient with peripheral neuropathy NCI-CTC Grade ≥ 3
• Patient with diarrhea NCI-CTC Grade ≥ 2
• Patient with acute or chronic pancreatitis
• Impaired cardiac function or clinically significant cardiac disease incl. unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug.
• Patients with clinically manifest diabetes mellitus, history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus
• Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BYL719	BYL719	In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene
BYL719 + fulvestrant	Fulvestrant	In post-menopausal patients with estrogen receptor positive locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene

Primary Outcome Measures

Name	Time	Method
Incidence rate of dose limiting toxicities (DLT).	5 years	MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.

Secondary Outcome Measures

Name	Time	Method
PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax.	5 years	PK parameter Cmax
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2)	5 years	PK parameter t1/2
Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant by measuring ORR.	5 years	Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline)
Progression-free survival at maximum tolerated dose	5 years	PFS at MTD
Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant	10 years	Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F.	5 years	PK parameter CL/F
Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F.	5 years	PK parameter Vz/F
PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf.	5 years	PK parameters AUC-tlast and AUC0-inf
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax.	5 years	PK parameter Tmax

Trial Locations

Locations (6)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Novartis Investigative Site; 🇬🇧 Oxford, United Kingdom

Vanderbilt Univeristy SC; 🇺🇸 Nashville, Tennessee, United States

UCSF Medical Center; 🇺🇸 San Francisco, California, United States

Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4); 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center/University of Texas MD Anderson; 🇺🇸 Houston, Texas, United States