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

NCT01219699 | Completed Phase 1 FDA Drug

• 2 other identifiers: CBYL719X21012010-018782-32
• Study Type: interventional
• Target: 221
• Locations: 5 countries
• Sites: 11

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

Conditions

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

Keywords

advanced solid tumors; mutation; amplification; wild type; PIK3CA gene; dose-escalation; estrogen receptor positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Incidence rate of dose limiting toxicities (DLT).

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

  5 years

Secondary Outcomes (9)

• Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant

  10 years

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

  5 years

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

  5 years

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

  5 years

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

  5 years

Study Arms (2)

BYL719

EXPERIMENTAL

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 + fulvestrant

EXPERIMENTAL

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

Interventions

BYL719 DRUG

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

BYL719

Fulvestrant DRUG

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

BYL719 + fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Univeristy SC

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center/University of Texas MD Anderson

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 38439079 DERIVED

• 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.

  PMID: 30543347 DERIVED

• 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.

  PMID: 29401002 DERIVED

• 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.

  PMID: 25002028 DERIVED

MeSH Terms

Interventions

Alpelisib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 13, 2010
• Study Start: October 5, 2010
• Primary Completion: February 5, 2015
• Study Completion: April 16, 2020
• Last Updated: September 22, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); US (5); NL (1); ES (2); GB (1)