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

NCT ID: NCT01219699

Last Updated: 2020-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-05
• Study Completion Date: 2020-04-16

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

BYL719

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: 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

Interventions

BYL719

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

UCSF Medical Center

San Francisco, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)

Nashville, Tennessee, United States

Vanderbilt Univeristy SC

Nashville, Tennessee, United States

MD Anderson Cancer Center/University of Texas MD Anderson

Houston, Texas, United States

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Würzburg, , Germany

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Novartis Investigative Site

Oxford, , United Kingdom

Countries

United States; Germany; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38439079 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30543347 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29401002 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25002028 (View on PubMed)

Other Identifiers

2010-018782-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBYL719X2101

Identifier Type: -

Identifier Source: org_study_id