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

September 21, 2020 updated by: Novartis Pharmaceuticals

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

221

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97080
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
  • United Kingdom
      • Oxford, United Kingdom, OX3 7LJ
        • Novartis Investigative Site
  • United States
    • California
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Univeristy SC
    • Texas
      • Houston, Texas, United States, 77030-4009
        • MD Anderson Cancer Center/University of Texas MD Anderson

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: BYL719
BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
Experimental: BYL719 + 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
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence rate of dose limiting toxicities (DLT).
Time Frame: 5 years
MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2010

Primary Completion (Actual)

February 5, 2015

Study Completion (Actual)

April 16, 2020

Study Registration Dates

First Submitted

October 6, 2010

First Submitted That Met QC Criteria

October 11, 2010

First Posted (Estimate)

October 13, 2010

Study Record Updates

Last Update Posted (Actual)

September 22, 2020

Last Update Submitted That Met QC Criteria

September 21, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBYL719X2101
  • 2010-018782-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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