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

Estrogen Receptor Positive Breast Cancer Clinical Trial

Official title:

A Phase IA, Multicenter, Open-label Dose Escalation Study of Oral BYL719, in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01219699
• Other study ID #: CBYL719X2101
• Secondary ID: 2010-018782-32
• Status: Completed
• Phase: Phase 1
• Start date: October 5, 2010
• Est. completion date: April 16, 2020

Study information

• Verified date: September 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: April 16, 2020
• Est. primary completion date: February 5, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors With an Alteration of the PIK3CA Gene
• Breast Neoplasms
• Estrogen Receptor Positive Breast Cancer
• Neoplasms

Intervention

Drug:
• BYL719
BYL719 is an oral a-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
• Fulvestrant
In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene. Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Wuerzburg
Netherlands	Novartis Investigative Site	Amsterdam
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
United Kingdom	Novartis Investigative Site	Oxford
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center/University of Texas MD Anderson	Houston	Texas
United States	Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)	Nashville	Tennessee
United States	Vanderbilt Univeristy SC	Nashville	Tennessee
United States	UCSF Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of dose limiting toxicities (DLT).	MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.	5 years
Secondary	Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant	Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.	10 years
Secondary	PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf.	PK parameters AUC-tlast and AUC0-inf	5 years
Secondary	PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax.	PK parameter Cmax	5 years
Secondary	Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax.	PK parameter Tmax	5 years
Secondary	Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F.	PK parameter CL/F	5 years
Secondary	Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F.	PK parameter Vz/F	5 years
Secondary	Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2)	PK parameter t1/2	5 years
Secondary	Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant by measuring ORR.	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)	5 years
Secondary	Progression-free survival at maximum tolerated dose	PFS at MTD	5 years