PI3K Inhibitor BYL719 in Combination With the HSP90 Inhibitor AUY922 in Patients With Advanced or Metastatic Gastric Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 11 January 2021
• Main ID: NCT01613950
• Date of registration: 31/05/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: PI3K Inhibitor BYL719 in Combination With the HSP90 Inhibitor AUY922 in Patients With Advanced or Metastatic Gastric Cancer
• Scientific title: A Phase IB, Multicenter, Open-label Dose Escalation Study of the PI3K Inhibitor BYL719 in Combination With the HSP90 Inhibitor AUY922 in Patients With Advanced or Metastatic Gastric Cancer Carrying a Molecular Alteration of PIK3CA or an Amplification of HER2
• Date of first enrolment: December 2012
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01613950
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Germany, Japan, Korea, Republic of, Switzerland, Taiwan, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal
junction;

- Patients must not have a complete gastrectomy;

- gastric tumors carrying PIK3CA mutation or amplification, or HER2-overexpression, or
both;

- at least one but no more than three previous lines of treatment for advanced or
metastatic disease;

- Patients with PIK3CA mutated or amplified tumors must have failed at least one line
but no more than three lines of standard chemotherapy and/or targeted agents;Patients
with HER2 amplified tumor must have failed at least one line, but no more than three
lines, with or without anti-HER2 therapy. All HER2 positive patients are expected to
have received trastuzumab unless contraindications were present or trastuzumab was
unavailable;

- Performance Status (PS) = 1 ;

- Adequate bone marrow, liver and other organ functions and laboratory parameters;

- Recovery from all AEs of previous anti-cancer therapies, including surgery and
radiotherapy, to baseline or to CTCAE Grade = 1, except for alopecia;Negative serum
pregnancy (ß hCG) test within 72 hrs before starting study treatment in all
pre-menopausal women and women < 12 months after the onset of menopause.

* Exclusion Criteria:

- Progressive disease during or after prior combination treatment with PI3K-inhibitors
and HSP90- inhibitors;

- history of prior significant toxicity from another PI3K- or HSP90- inhibitor requiring
discontinuation of treatment;

- primary CNS tumor or uncontrolled CNS metastasest;

- Patients who are currently receiving medication with a known risk of prolonging the QT
interval or inducing Torsades de Pointes and the treatment cannot either be
discontinued or switched to a different medication prior to starting study drug
treatment;

- Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs
or with fasting glucose = 140 mg/dL / 7.8 mmol/L, history of clinically significant
gestational diabetes mellitus or documented steroid-induced diabetes mellitus;Patients
with diarrhea CTCAE Grade = 2 ;

- Patients with acute or chronic pancreatitis; History or current evidence of central
serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy as assessed
by ophthalmologic examination at baseline that would be considered a risk factor for
CSR/RVO;

- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of oral BYL719;

- Patients receiving chronic slow-release formulation of Proton Pump Inhibitors (PPI),
H2-antagonists or other gastric pH elevating agents;

- Treatment with therapeutic doses of coumarin-based anticoagulants (e.g., warfarin
sodium, Coumadin®). Low doses of courmarin-based anticoagulants;

- Patients receiving chronic or high dose corticosteroids therapy; other
protocol-defined inclusion/exclusion criteria may apply.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein

Intervention(s)

Drug: AUY922

Drug: BYL719

Primary Outcome(s)

Incidence rate of Dose Limiting Toxicities. [Time Frame: cycle 1]

Secondary Outcome(s)

Progression free survival (PFS) as per RECIST version 1.1 [Time Frame: every 6 weeks]

Best Overall Response (BOR) as per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 [Time Frame: every 6 weeks]

Frequency of adverse events (AEs) [Time Frame: duration of the study, an expected average of 24 months]

Overall survival rate at 6 months (OS6) [Time Frame: 6 months]

Overall survival (OS) [Time Frame: approximately 1 year]

Plasma concentration versus time profiles of BYL719 as single agent an in combination with AUY922. [Time Frame: 2 months]

Frequency and severity of serious adverse events (SAEs) [Time Frame: duration of the study, an expected average of 24 months]

Severity of adverse events (AEs) [Time Frame: duration of the study, an expected average of 24 months]

Plasma concentration versus time profile of AUY922 as single agent and in combination with BYL719 [Time Frame: 2 months]

Plasma concentration versus time profile of the AUY922 metabolite BJP762 [Time Frame: 2 months]

Overall response rate (ORR) as per RECIST version 1.1 [Time Frame: an expected average of 12 months]

Secondary ID(s)

2011-005978-40

CBYL719X2103

Source(s) of Monetary Support

Please refer to primary and secondary sponsors