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Advanced Solid Tumors With an Alteration of the PIK3CA GenePhase 1NCT01219699

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

A Phase 1 study testing BYL719 and Fulvestrant in people with Advanced Solid Tumors With an Alteration of the PIK3CA Gene and Estrogen Receptor Positive Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BYL719 and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
221 participants
Where
11 sitesin 5 countries
Study dates
5 Oct 2010to 16 Apr 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 9Show fewer
  • 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

Trial locations and contacts

11 sites in 5 countries.

11 sites in 5 countries

United States5 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • MD Anderson Cancer Center/University of Texas MD Anderson

    Houston, Texas, 77030-4009

  • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)

    Nashville, Tennessee, 37203

  • Vanderbilt Univeristy SC

    Nashville, Tennessee, 37232

  • UCSF Medical Center

    San Francisco, California, 94143

Other trials in United States

Germany2 sites

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

Other trials in Spain

Netherlands1 site

  • Novartis Investigative Site

    Amsterdam, 1066 CX

Other trials in Netherlands

United Kingdom1 site

  • Novartis Investigative Site

    Oxford, OX3 7LJ

Other trials in United Kingdom

About this study

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

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

Being tested
BYL719, Fulvestrant
Keywords
advanced solid tumors, mutation, amplification, wild type, PIK3CA gene, dose-escalation, estrogen receptor positive breast cancer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BYL719Drug

    BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.

  • FulvestrantDrug

    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

Study groups in NCT01219699
Study groupRoleWhat they receive
BYL719ExperimentalIn 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
Receives: Drug: BYL719
BYL719 + fulvestrantExperimentalIn 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
Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence rate of dose limiting toxicities (DLT).

    MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.

    Measured: 5 years

Secondary outcomes (9)

  1. 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.

    Measured: 10 years

  2. PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf.

    PK parameters AUC-tlast and AUC0-inf

    Measured: 5 years

  3. PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax.

    PK parameter Cmax

    Measured: 5 years

  4. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax.

    PK parameter Tmax

    Measured: 5 years

  5. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F.

    PK parameter CL/F

    Measured: 5 years

  6. Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F.

    PK parameter Vz/F

    Measured: 5 years

  7. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2)

    PK parameter t1/2

    Measured: 5 years

  8. 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)

    Measured: 5 years

  9. Progression-free survival at maximum tolerated dose

    PFS at MTD

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2010 (estimated)
  2. Study start5 Oct 2010
  3. Primary completion5 Feb 2015
  4. Study completion16 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
221 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01219699
Sponsor's protocol ID
CBYL719X2101
Other IDs
2010-018782-32
Status last verified
Sep 2020
First submitted
6 Oct 2010
Last updated
22 Sep 2020
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rodon J, Demanse D, Rugo HS, Burris HA, Simo R, Farooki A, Wellons MF, Andre F, Hu H, Vuina D, Quadt C, Juric D. A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer. Breast Cancer Res. 2024 Mar 4;26(1):36. doi: 10.1186/s13058-024-01773-1.

    PubMed 38439079

  • Juric D, Janku F, Rodon J, Burris HA, Mayer IA, Schuler M, Seggewiss-Bernhardt R, Gil-Martin M, Middleton MR, Baselga J, Bootle D, Demanse D, Blumenstein L, Schumacher K, Huang A, Quadt C, Rugo HS. Alpelisib Plus Fulvestrant in PIK3CA-Altered and PIK3CA-Wild-Type Estrogen Receptor-Positive Advanced Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):e184475. doi: 10.1001/jamaoncol.2018.4475. Epub 2019 Feb 14.

    PubMed 30543347

  • Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, Rugo HS, Seggewiss-Bernhardt R, Huang A, Bootle D, Demanse D, Blumenstein L, Coughlin C, Quadt C, Baselga J. Phosphatidylinositol 3-Kinase alpha-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study. J Clin Oncol. 2018 May 1;36(13):1291-1299. doi: 10.1200/JCO.2017.72.7107. Epub 2018 Feb 5.

    PubMed 29401002

  • Vora SR, Juric D, Kim N, Mino-Kenudson M, Huynh T, Costa C, Lockerman EL, Pollack SF, Liu M, Li X, Lehar J, Wiesmann M, Wartmann M, Chen Y, Cao ZA, Pinzon-Ortiz M, Kim S, Schlegel R, Huang A, Engelman JA. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014 Jul 14;26(1):136-49. doi: 10.1016/j.ccr.2014.05.020. Epub 2014 Jul 4.

    PubMed 25002028

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BYL719 and Fulvestrant in people with Advanced Solid Tumors With an Alteration of the PIK3CA Gene and Estrogen Receptor Positive Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Germany, Spain, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence rate of dose limiting toxicities (DLT). (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01219699, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2020.

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