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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
221

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 5, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 5, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 6, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 13, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 22, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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