AzTrials
AzTrials

HER2-positive Breast CancerPhase 1NCT02038010

BYL719 + T-DM1 in HER2(+) Metastatic Breast Cancer Pts Who Progress on Prior Trastuzumab & Taxane Tx

A Phase 1 study testing PI3K inhibitor BYL719, ado-trastuzumab emtansine and pharmacological study in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by Northwestern University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to see whether a combination of two different drugs - trastuzumab-MCC-DM1 (T-DM1) and BYL719 is safe, and if it might be effective in treating metastatic breast cancer. T-DM1 is a type of drug that contains an antibody (trastuzumab) linked to chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
PI3K inhibitor BYL719, ado-trastuzumab emtansine and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
21 May 2014to 20 May 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically-confirmed HER2-positive breast cancer that is locally advanced or metastatic (stage 4); ideally this should be from biopsy of the metastatic disease; however if this is not available, histologic confirmation from the primary tumor is acceptable
  • Patients must have had progression on a trastuzumab and taxane-based chemotherapy regimen during or after treatment for locally advanced or metastatic disease or within 6 months after treatment for early-stage HER2-positive disease documented by one of the following results using Food and Drug Administration (FDA)-approved testing methods:
  • Fluorescence in situ hybridization (FISH)-positive (with an amplification ratio >= 2.0 indicating positive status) and/or
  • Immunohistochemistry (IHC) 3 + by local laboratory assessment
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patients must have a life expectancy >= 90 days
Show all 19Show fewer
  • Patients must have baseline laboratory tests within the following parameters at least 4 weeks (28 days) prior to registration:
  • Hemoglobin > 8 g/dL (which may be reached by transfusion)
  • Platelet count >= 100 x 10^9/L (no transfusion allowed within 2 weeks)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without growth factor support
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or =< 5 x ULN if liver metastases are present
  • Serum creatinine =< 1.5 x ULN or calculated or directly measured creatinine clearance (CrCl) >= 50% LLN (lower limit of normal)
  • Fasting plasma glucose (FPG) < 140 mg/dL/7.8 mmol/L
  • Patients with child-bearing potential must have a negative urine pregnancy test within 7 days prior to registration
  • Patients must have a baseline electrocardiogram (ECG) showing QT interval =< 460 msec within 14 days prior to registration
  • Patients must provide written informed consent prior to any registration on study
  • Patients must be willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Patient must be able to swallow and retain oral medication

Who cannot join

  • Patients with prior sensitivity or intolerance to PI3K inhibitors are not eligible for participation
  • Patients with a history of grade >= 3 hypersensitivity reaction to trastuzumab, OR grade >= 1 with the most recent trastuzumab infusion before study entry, OR continued requirement for prolonged trastuzumab infusions to prevent hypersensitivity reactions are not eligible for participation
  • Patients with a history of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued are not eligible for participation
  • Patients who have received prior treatment with T-DM1 are not eligible for participation
  • Patients who have received prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to registration are not eligible for participation
  • Patients with central nervous system (CNS) involvement may participate if the patient meets all of the following criteria:
Show all 34Show fewer
  • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
  • Clinically stable with respect to the CNS tumor at the time of screening
  • Not receiving steroid therapy
  • Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases
  • Patients who have received radiotherapy =< 4 weeks prior to registration, with the exception of palliative radiotherapy, who have not recovered from side effects of such therapy to baseline or grade =< 1 and/or from whom >= 30% of the bone marrow was irradiated are not eligible for participation
  • Patients who have undergone major surgery =< 4 weeks prior to registration or who have not recovered from side effects of such procedure are not eligible for participation
  • Patients with clinically significant cardiac disease or impaired cardiac function are not eligible for participation; this includes patients with:
  • Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= 2)
  • Left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings)
  • History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality (e.g. congenital long QT syndrome, high-grade/complete atrioventricular [AV]-blockage)
  • Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), < 3 months prior to screening
  • QT interval adjusted according to Fridericia (QTcF) > 460 msec on screening ECG
  • Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose (FPG) >= 140 mg/dL/7.8 mmol/L, or history of documented steroid-induced diabetes mellitus are not eligible for participation
  • Patients exhibiting any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures are not eligible for participation; this might include, but is not limited to, infection/inflammation, intestinal obstruction, and/or social/psychological complications
  • Patients with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) are not eligible for participation
  • Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) AND are unable to discontinue this medication or switch to a different medication prior to beginning study treatment are not eligible for participation
  • Patients with a history of another malignancy within 2 years prior to registration are not eligible for participation; NOTE: the exceptions to this include cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
  • Patients receiving therapeutic doses of warfarin are not eligible for participation; NOTE: Patients with a need for therapeutic anticoagulation should be given low molecular weight heparin or other non-warfarin product
  • Pregnant or nursing (lactating) women are not eligible for participation; NOTE: Pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not eligible for participation UNLESS they agree to use highly effective methods of contraception during dosing and for 5 weeks after study drugs discontinuation; highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 5 weeks before receiving study treatment. In case of oophorectomy alone, the reproductive status of the woman must have been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject
  • Combination of the following:
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • NOTE: Oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the sole method of contraception, as BYL719 has not been characterized with respect to its potential to interfere with the PK and/or the effectiveness of OCs

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: A Phase I Study of BYL719 and Trastuzumab-MCC-DM1 in HER2-Positive Metastatic Breast Cancer Patients With Progression on Prior Trastuzumab and Taxane-Based Therapy

The purpose of this study is to see whether a combination of two different drugs - trastuzumab-MCC-DM1 (T-DM1) and BYL719 is safe, and if it might be effective in treating metastatic breast cancer. T-DM1 is a type of drug that contains an antibody (trastuzumab) linked to chemotherapy. The antibody in T-DM1 targets a marker on breast cancer cells called HER2, which allows the drug to go directly to the cancer cells. The use of T-DM1 in this study is considered standard treatment for the type of cancer in this study. Participants in this study have already been treated with trastuzumab and chemotherapy in the past, and their cancer has gotten worse in spite of those treatments. BYL719 is an oral drug (taken by mouth) that the researchers think may help T-DM1 to work better.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine safety, tolerability, feasibility, and the maximum-tolerated dose (MTD) of dose-escalating BYL719 in combination with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer (MBC) after progression on trastuzumab and taxane-based therapy.

SECONDARY OBJECTIVES:

  1. Evaluate pharmacokinetics (PK) of BYL719 administered in combination with T-DM1.

II. Assess any preliminary evidence of efficacy of BYL719 and T-DM1 in combination in patients with HER2-positive MBC.

TERTIARY OBJECTIVES:

  1. Explore efficacy in patients whose tumors have an alteration (mutation or amplification) of the PIK3CA gene and decrease of phosphatase and tensin homolog gene (PTEN) expression. (Optional) II. Examine other v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) downstream markers by immunohistochemistry. (Optional)

OUTLINE: This is a dose-escalation study of PI3K inhibitor BYL719.

Patients receive PI3K inhibitor BYL719 orally (PO) daily on days 1-21 and ado-trastuzumab emtansine (T-DM1) intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity, or at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 3 months.

Being tested
PI3K inhibitor BYL719, ado-trastuzumab emtansine, pharmacological study, laboratory biomarker analysis
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PI3K inhibitor BYL719Drug

    Also called BYL719, phosphoinositide 3-kinase inhibitor BYL719

    Given PO

  • ado-trastuzumab emtansineBiological

    Also called Kadcyla, T-DM1, trastuzumab-DM1, trastuzumab-MCC-DM1

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Optional correlative studies

Study groups in NCT02038010
Study groupRoleWhat they receive
Treatment (PI3K inhibitor BYL719, ado-trastuzumab emtansine)ExperimentalPatients receive PI3K inhibitor BYL719 PO daily on days 1-21 and ado-trastuzumab emtansine IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: PI3K inhibitor BYL719; Biological: ado-trastuzumab emtansine; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT) of Dose-escalating BYL719 in Combination With T-DM1

    DLTs of BYL719 in combination with T-DM1 will be assessed using National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (except for hyperglycemia). A DLT is described any grade 3 or higher, clinically significant toxicity (excluding alopecia) experienced during the first 21 days following first dose of BYL719 that is determined to be at least possibly related to study medication. Lower grades may also be considered DLTs if they lead to a dose interruption of more than 7 consecutive days of BYL719. In general adverse events (AEs) will be graded according to the following:

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

    Measured: The 1st 21 days (Cycle 1) of treatment

  2. Maximum Tolerated Dose (MTD) of BYL719 in Combination With T-DM1.

    Safety of BYL719 in combination with T-DM1 will be assessed during the first 21 days (1 cycle=21 days) which will assist in providing the MTD. Adverse Events including dose limiting toxicities (DLT), changes in physical findings, or clinical laboratory results as well as cardiac toxicity (changes in cardiac function, which will be measured by use of echocardiogram or MUGA scan) will be evaluated.

    For each dose level, 3 patients will be treated. If none (0 of 3) show a DLT, dose will be escalated for the next cohort of patients.

    If 2 or 3 have a DLT, then the previous dose will be considered the MTD. If 2 or 3 in cohort 1 (starting dose) experience a DLT, then the dose in -1 cohort will be used.

    If 1 of 3 patients has a DLT, then an additional 3 patients will be added to that dose level.

    If 1 of 6 has a DLT, then the dose will be escalated. If 2 of 6 have a DLT, then this dose will be considered the MTD. If 3 or more of 6 have a DLT, then the previous dose will be the MTD.

    Measured: The 1st 21 days (Cycle 1) of treatment

Secondary outcomes (3)

  1. Pharmacokinetics (PK) of BYL719 Administered in Combination With T-DM1.

    To assess the pharmacokinetics (PK)of BYL719, blood will be drawn from patients on Day 1, 8, and 15 of Cycles 1, 2 and 3 where 1 Cycle = 21 days. After that blood will be drawn once every 3 cycles. PK parameters of BYL719 including peak and trough concentrations as an estimate of the steady-state concentration, elimination clearance, interindividual variability of the elimination clearance, and the effect of PK parameters with prolonged administration of BYL719 will be obtained. Steady state concentration will be analyzed to see if there is any relationship with efficacy or toxicity.

    Measured: Day 1, 8, and 15 of Cycles 1, 2, and 3, then every 3 Cycles (1 Cycle =21 days) while on treatment where the median number of cycles is 11 and range is 3-19 cycles.

  2. Progression-Free Survival (PFS) of BYL719 Administered in Combination With T-DM1 for All Patients Treated on Study.

    Progression-Free Survival (PFS) for patients treated with BYL719 and T-DM1 in combination is measured for all patients from the time of treatment initiation until the first documentation of progressive disease or death from any cause. It will be assessed every 3 months up to 1 year after discontinuation of the study drugs. Patients that completed at least 3 cycles of treatment and had imaging at 1st response time point were considered evaluable for this objective.

    Measured: From the start of treatment and every 3 months up to 1 year after discontinuation of treatment. 1 Cycle = 21 days. Median number of cycles is 11 and range is 3-19 cycles.

  3. Objective Response Rate (ORR) of BYL719 Administered in Combination With T-DM1 by Cohort

    ORR for patients treated with BYL719 in combination with T-DM1 assessed every 3 cycles (every 9 weeks) with imaging and Best Response defined by RECIST v1.1. ORR is defined as number of patients with Complete Response (CR)+Partial Response (PR) documented as their Best Response (confirmed 4 weeks later). Response is based on evaluation of target and non-target lesions. Clinical lesions will only be considered measurable when they are superficial. Patients that completed at least 3 cycles of treatment and had imaging at 1st response time point were considered evaluable for this objective.

    Target Lesions:

    CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.

    For Non-Target Lesions:

    CR: Disappearance of all non-target lesions and normalization of tumor marker level Non-complete Response (Non-CR): Persistence of one or more non-target lesion(s)

    Measured: From the start of treatment and every 3 cycles during treatment where 1 cycle =21 days, median number of cycles is 11 and range of cycles is 3-19.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2014 (estimated)
  2. Study start21 May 2014
  3. Primary completion15 Apr 2015
  4. Study completion20 May 2017

Resources

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02038010
Sponsor's protocol ID
NU 13B06
Other IDs
NCI-2013-02224, NU 13B06, P30CA060553, STU00087202
Status last verified
Jun 2020
First submitted
14 Jan 2014
Last updated
29 Jun 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PI3K inhibitor BYL719, ado-trastuzumab emtansine and pharmacological study in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by Northwestern University at 1 site in United States.

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 19 inclusion and 34 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 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 4 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dose Limiting Toxicity (DLT) of Dose-escalating BYL719 in Combination With T-DM1 (time frame: The 1st 21 days (Cycle 1) of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02038010.

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 29 Jun 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in