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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01219699
First received: October 6, 2010
Last updated: May 27, 2014
Last verified: May 2014

October 6, 2010
May 27, 2014
October 2010
December 2014   (final data collection date for primary outcome measure)
MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant [ Time Frame: February 2013 ] [ Designated as safety issue: Yes ]
Incidence rate of dose limiting toxicities (DLT) (in the first cycle (of 28 days) of each investigated dose level).
To determine the MTD (or RP2D) of oral BYL719 as single agent in adult patients with advanced solid malignancies whose tumors have a mutation of the PIK3CA gene. [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01219699 on ClinicalTrials.gov Archive Site
  • Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: Yes ]
    Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.
  • Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: No ]
    plasma concentration-time profiles and derived basic PK parameters of BYL719, including but not limited to AUC0-tlast, AUC0-inf, Cmax, Tmax, CL/F, Vz/F and the terminal half-life (t1/2) and other PK parameters if deemed appropriate.
  • Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: No ]
    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)
  • Assess the overall safety and tolerability of BYL719 treatment in all patients by type, intensity, severity and seriousness of adverse events. [ Time Frame: May 2012 ] [ Designated as safety issue: Yes ]
  • To assess PI3K pathway inhibition in skin measuring pS6 and tumor measuring pS6 and pAkt [ Time Frame: May 2012 ] [ Designated as safety issue: No ]
  • To determine the BYL719 plasma concentration-time profiles of oral BYL719 at several time-points and derived basic PK paramenters suac as AUC, Cmax, and t1/2. [ Time Frame: May 2012 ] [ Designated as safety issue: No ]
  • To assess clinical tumor response of oral BYL719 in patients with relapsing/refractory PIK3CA mutant solid yumors by RECIST [ Time Frame: May 2012 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene
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

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Solid Tumors With an Alteration of the PIK3CA Gene
  • Estrogen Receptor Positive Breast Cancer
  • Drug: BYL719
    BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
  • 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

  • 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
    Intervention: Drug: BYL719
  • 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
    Intervention: Drug: Fulvestrant
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
200
December 2014
December 2014   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Netherlands,   Spain,   United Kingdom
 
NCT01219699
CBYL719X2101, 2010-018782-32
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP