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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Stomach Neoplasms; Esophageal Neoplasms; Metastatic Gastric Cancer; Mutated PI3KCA Protein; Overexpressed HER2 Protein;

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Trial Information

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


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 (β 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence rate of Dose Limiting Toxicities.

Outcome Description:

To determine the maximum tolerated dose (MTD) and/or Recommended dose for expansion (RDE) and schedule of BYL719 and AUY922 when used as a combination in patients with advanced or metastatic gastric cancer carrying a molecular alteration of PIK3CA and/or an amplification of HER2. 1 cycle = 28days

Outcome Time Frame:

cycle 1

Safety Issue:

Yes

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

CBYL719X2103

NCT ID:

NCT01613950

Start Date:

December 2012

Completion Date:

July 2014

Related Keywords:

  • Stomach Neoplasms; Esophageal Neoplasms; Metastatic Gastric Cancer; Mutated PI3KCA Protein; Overexpressed HER2 Protein;
  • gastric cancer; advanced gastric or metastatic gastric cancer; PI3K; PIK3CA mutation; Her2 amplification; HSP90 inhibitor; PI3K inhibitor; PIK3CA amplification
  • Neoplasms
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Stomach Neoplasms
  • Neoplasms, Second Primary

Name

Location

Massachusetts General Hospital Mass General 2Boston, Massachusetts  02114
MD Anderson Cancer Center/University of Texas Gastrointestinal Med. OncologyHouston, Texas  77030-4009
University of California at Los Angeles SC-5Los Angeles, California  90095