Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 ProteinPhase 1NCT01613950
PI3K Inhibitor BYL719 in Combination With the HSP90 Inhibitor AUY922 in Patients With Advanced or Metastatic Gastric Cancer
A Phase 1 study testing AUY922 and BYL719 in people with Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein, run by Novartis Pharmaceuticals at 9 sites in 6 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein
- What is being tested?
- AUY922 and BYL719
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 9 sitesin 6 countries
- Study dates
- Dec 2012to Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
United States2 sites
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, 02114
University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
Houston, Texas, 77030-4009
Germany2 sites
Novartis Investigative Site
Cologne, 50924
Novartis Investigative Site
Würzburg, 97080
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 110 744
Novartis Investigative Site
Seoul, 738-736
About this study
Official 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
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.
- Being tested
- AUY922, BYL719
- Keywords
- gastric cancer advanced gastric or metastatic gastric cancer PI3K PIK3CA mutation Her2 amplification HSP90 inhibitor PI3K inhibitor PIK3CA amplification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922Drug
AUY922 is a non-geldanamycin inhibitor of the heat shock protein 90 (HSP90).
BYL719Drug
BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| BYL719 + AUY922 | Experimental | 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. Receives: Drug: AUY922; Drug: BYL719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of Dose Limiting Toxicities.
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
Measured: cycle 1
Secondary outcomes (11)
Frequency of adverse events (AEs)
To characterize the safety and tolerability of BYL719 and AUY922 in combination.
Measured: duration of the study, an expected average of 24 months
Best Overall Response (BOR) as per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
To assess the preliminary anti-tumor activity of BYL719/AUY922 combination from Treatment start to disease progression
Measured: every 6 weeks
Plasma concentration versus time profiles of BYL719 as single agent an in combination with AUY922.
To determine the single dose PK of BYL719 single dose, and multiple doses PK of BYL719.
Measured: 2 months
Overall response rate (ORR) as per RECIST version 1.1
To assess the preliminary anti-tumor activity of BYL719/AUY922 combination.
Measured: an expected average of 12 months
Progression free survival (PFS) as per RECIST version 1.1
To assess the preliminary anti-tumor activity of BYL719/AUY922 combination.
Measured: every 6 weeks
Overall survival (OS)
To assess the preliminary anti-tumor activity of BYL719/AUY922 combination.
Measured: approximately 1 year
Overall survival rate at 6 months (OS6)
To assess the preliminary anti-tumor activity of BYL719/AUY922 combination.
Measured: 6 months
Frequency and severity of serious adverse events (SAEs)
To characterize the safety and tolerability of BYL719 and AUY922 in combination.
Measured: 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
To determine the single dose and multiple dose pharmacokinetics of AUY922
Measured: 2 months
Plasma concentration versus time profile of the AUY922 metabolite BJP762
To determine pharmacokinetics of BJP762 after single dose and multiple dose of AUY922
Measured: 2 months
Severity of adverse events (AEs)
To characterize the safety and tolerability of BYL719 and AUY922 in combination.
Measured: duration of the study, an expected average of 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2012 (estimated)
- Study startDec 2012
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 ProteinStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01613950
- Sponsor's protocol ID
- CBYL719X2103
- Other IDs
- 2011-005978-40
- Status last verified
- Feb 2017
- First submitted
- 31 May 2012
- Last updated
- 9 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01613950
- Acronym / sponsor ID
- CBYL719X2103
- Keywords
- gastric cancer advanced gastric or metastatic gastric cancer PI3K PIK3CA mutation Her2 amplification HSP90 inhibitor PI3K inhibitor PIK3CA amplification
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 7 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BYL719 + AUY922 | Experimental | Drug: AUY922, Drug: BYL719Dose 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (10 listed)
- 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 ;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AUY922AUY922 is a non-geldanamycin inhibitor of the heat shock protein 90 (HSP90). | Drug | BYL719 + AUY922 |
| BYL719BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor. | Drug | BYL719 + AUY922 |
Primary outcome
Incidence rate of Dose Limiting Toxicities.
Time frame: cycle 1
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
11 secondary outcomes
Frequency of adverse events (AEs)
Time frame: duration of the study, an expected average of 24 months
Best Overall Response (BOR) as per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time frame: every 6 weeks
Plasma concentration versus time profiles of BYL719 as single agent an in combination with AUY922.
Time frame: 2 months
Overall response rate (ORR) as per RECIST version 1.1
Time frame: an expected average of 12 months
Progression free survival (PFS) as per RECIST version 1.1
Time frame: every 6 weeks
Overall survival (OS)
Time frame: approximately 1 year
Overall survival rate at 6 months (OS6)
Time frame: 6 months
Frequency and severity of serious adverse events (SAEs)
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
Severity of adverse events (AEs)
Time frame: duration of the study, an expected average of 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Results for CBYL719X2103 can be found on the Novartis Clinical Trials websiteLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AUY922 and BYL719 in people with Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein, run by Novartis Pharmaceuticals at 9 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Germany, South Korea, Japan, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence rate of Dose Limiting Toxicities. (time frame: cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.