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

NCT ID: NCT01613950

Last Updated: 2020-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2014-03-31

Brief Summary

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The study is intended to investigate the safety of BYL719 and AUY922 in patients with advanced gastric cancer, and to determine the MTD and/or RDE of both drugs in combination. In addition, the preliminary efficacy of BYL719 in combination with AUY922, and the pharmacokinetics of both drugs will be assessed. Patients will be eligible for this study, if their tumors carry either a molecular alteration of PIK3CA, or an amplification of HER2.

The study includes a dose escalation part followed by a safety expansion phase.

Detailed Description

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Conditions

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

Keywords

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gastric cancer advanced gastric or metastatic gastric cancer PI3K PIK3CA mutation Her2 amplification HSP90 inhibitor PI3K inhibitor PIK3CA amplification

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BYL719 + AUY922

Dose finding study to estimate the maximum tolerated dose(s) (MTD) and/or recommended dose(s) for safety expansion (RDE) followed by an expansion phase to further assess the safety and preliminary activity of the combination. BYL719 tablets will be administered orally on a daily schedule (q.d.). a b.i.d. regimen may be explored. AUY922 will be administered by IV infusion once per week.

Group Type EXPERIMENTAL

AUY922

Intervention Type DRUG

AUY922 is a non-geldanamycin inhibitor of the heat shock protein 90 (HSP90).

BYL719

Intervention Type DRUG

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

Interventions

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AUY922

AUY922 is a non-geldanamycin inhibitor of the heat shock protein 90 (HSP90).

Intervention Type DRUG

BYL719

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

Intervention Type DRUG

Eligibility Criteria

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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;
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Massachusetts General Hospital Mass General 2

Boston, Massachusetts, United States

Site Status

University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology

Houston, Texas, United States

Site Status

Novartis Investigative Site

Cologne, , Germany

Site Status

Novartis Investigative Site

Würzburg, , Germany

Site Status

Novartis Investigative Site

Chuo-ku, Tokyo, Japan

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Bellinzona, , Switzerland

Site Status

Novartis Investigative Site

Taipei, , Taiwan

Site Status

Countries

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United States Germany Japan South Korea Switzerland Taiwan

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13567

Results for CBYL719X2103 can be found on the Novartis Clinical Trials website

Other Identifiers

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2011-005978-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBYL719X2103

Identifier Type: -

Identifier Source: org_study_id