Her2 Positive Metastatic Breast CancerPhase 1/2NCT01495884
The Myocet/Lapatinib Study. ICORG 10-03, V5
A Phase 1/2 study testing non-pegylated liposomal doxorubicon (Myocet™) and Lapatinib (Tyverb™) in people with Her2 Positive Metastatic Breast Cancer, run by Cancer Trials Ireland at 10 sites in Ireland.
Trial summary
This study is a Phase I/II open label, multi-centre trial. Patients with HER2+ve metastatic breast cancer, following disease progression during, or after, treatment with trastuzumab and taxanes, will be treated with Lapatinib (Tyverb™ 500-1250 mg orally daily - depending on the maximum tolerated dose (MTD) determined… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Her2 Positive Metastatic Breast Cancer
- What is being tested?
- non-pegylated liposomal doxorubicon (Myocet™) and Lapatinib (Tyverb™)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 10 sitesIreland
- Study dates
- Mar 2011to Oct 2014
- Phase
- Phase 1/2
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
- Written informed consent obtained prior to any study-related procedures.
- Female patients, age ≥ 18 years, who are either post menopausal (post-menopausal status will be defined as patients who are amenorrheic for > 1 year or for a shorter duration if FSH, LH and/or oestradiol levels are within the post-menopausal range), surgically sterile or practicing an effective method of birth control agreed with the patients study physician. Women of childbearing potential should use an effective contraceptive ( such as non hormonal intra uterine device (IUD), condoms, sexual abstinence or vasectomised partner).during treatment and up to 6 months following discontinuation of therapy.
- Histologically confirmed metastatic breast cancer
- Documented HER2 overexpression (IHC 3+ or FISH or CISH positive)
- At least one measurable lesion according to RECIST criteria. Patients with bone only disease are not eligible.
- Patients with controlled brain metastasis are eligible.
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- Documented disease progression. Progression for entry is defined as appearance of any new lesion not previously identified or increase of 25% or more in existent lesion from previous CT scan and must be documented
- Prior treatment must have contained trastuzumab and taxane. Patients may have been treated with Lapatinib previously.
- Life expectancy of at least 12 weeks
- ECOG Performance Status of ≤ 2
- Left ventricular ejection fraction (LVEF) ≥ 55%, as measured by Echocardiogram or MUGA Scan (within 14 days prior to first infusion), and no documented history of uncontrolled or symptomatic angina, arrhythmias or congestive heart failure within the previous 6 months
- Adequate bone marrow, haematological, hepatic and renal function defined as:
- Absolute Neutrophils Count ≥ 1.5 x 109/L
- Platelet Count ≥ 100 x 109/L
- Haemoglobin ≥ 9.0 g/dL
- Calculated creatinine clearance ≥ 40 mL/min
- Total bilirubin ≤ ULN. Patients with Gilbert's syndrome prior to study entry must have total bilirubin < 3 x ULN.
- Alkaline Phosphatase and AST or ALT within the parameters specified in protocol
- Patients must have recovered from clinically significant side effects associated with prior radiotherapy and chemotherapy
- Able to swallow and retain oral medication.
- Formalin-fixed paraffin-embedded tissue from archived tumour tissue samples available (from the primary or metastatic tissue.
- Patients meeting any of the following exclusion criteria are not eligible for enrolment into this study:
Who cannot join
- Pregnant or lactating women
- Prior anthracycline chemotherapy with a lifetime dose exceeding 360 mg/m2 doxorubicin or 550 mg/m2 epirubicin
- Documented history of poorly controlled hypertension), arrhythmia, clinically significant valvular disease, angina requiring treatment, transmural infarction, myocardial infarction within the previous 6 months
- Concurrent disease that would make the patient inappropriate for study participation, or any other serious medical disorder that would interfere with the patient's safety
- Dementia, altered mental status, or any other psychiatric condition that would interfere with the patient's safety or informed consent
- Active or uncontrolled bacterial, viral or fungal infection.
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- History of other malignancy. However patients who have been disease free for 5 years, or patients with a history of resected non-melanoma skin cancer or successfully treated in situ cancer are eligible
- Concurrent cancer therapy (chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or within 4 weeks preceding the first dose of investigational product)
- Unresolved or unstable, serious toxicity from prior administration of another investigational product
- Concurrent treatment with an investigational drug within 4 weeks preceding the first dose of investigational product
- Known hypersensitivity to lapatinib and Myocet™ or their excipients
- Any other contraindications for lapatinib and Myocet™
- Receive concurrent treatment with prohibited medications. Zometa for patients with bone metastasis is allowed. If the patient is on Zometa at start of the study, it should be continued throughout the duration of the study.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Ireland10 sites
Bon Secours Hospital
Cork
Cork University Hospital
Cork
Beaumont Hospital
Dublin
Mater Misercordiae University Hospital
Dublin
Mater Private Hospital
Dublin
St James's Hospital
Dublin
St. Vincent's University Hospital
Dublin
University Hospital Galway
Galway
University Hospital Limerick
Limerick
Waterford Regional Hospital
Waterford
About this study
Official title: A Phase I/II Study of Lapatinib Plus Myocet TM in Patients With HER2+ve Metastatic Breast Cancer Following Disease Progression During, or After, Treatment With Trastuzumab and Taxanes
This study is a Phase I/II open label, multi-centre trial. Patients with HER2+ve metastatic breast cancer, following disease progression during, or after, treatment with trastuzumab and taxanes, will be treated with Lapatinib (Tyverb™ 500-1250 mg orally daily - depending on the maximum tolerated dose (MTD) determined in the Phase I part of the study) plus Myocet™, 50-60 mg/m2 i.v q3 weeks).
Within the Phase I part, doses are assigned at registration according to the dose escalation scheme.
Read more
The dose for the Phase II part of the trial will be based on the MTD established in the Phase I part of the study.
Clinical and laboratory parameters will be assessed to evaluate disease response and toxicity of study therapy. Safety assessments will be performed every 3 weeks for the first 24 weeks. Efficacy assessments (radiological examination) will be performed on all patients every 8 weeks (± 7 days) for the first 24 weeks. Cardiotoxicity assessments will be performed at weeks 6 and 12. From week 24, safety, efficacy and cardiotoxicity assessments will be performed every 12 weeks and at the end of treatment (disease progression, unacceptable toxicity or patient withdraws consent).
Read the detailed description
Primary Objective:
- To determine the optimal dose for lapatinib plus Myocet™, in combination, in patients with HER2-positive metastatic breast cancer following disease progression during, or after, treatment with trastuzumab and taxanes (Phase I).
- To evaluate the 6 month progression-free survival of patients with HER2-positive metastatic breast cancer, following disease progression during, or after, treatment with trastuzumab and taxanes, who are treated with lapatinib plus Myocet™ (Phase II plus patients treated at MTD in Phase I).
Secondary Objectives:
- To evaluate the overall survival time, duration of progression -free survival, time to treatment failure, confirmed tumour response rate and duration of response in patients treated with this regimen (Phase II plus patients treated at MTD in Phase I).
- To assess the safety and tolerability of this regimen in these patients.
- To assess the incidence of cardiotoxicity in these patients treated with this regimen.
- Conditions
- Her2 Positive Metastatic Breast Cancer
- Being tested
- non-pegylated liposomal doxorubicon (Myocet™), Lapatinib (Tyverb™)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-pegylated liposomal doxorubicon (Myocet™)Drug
Lapatinib (Tyverb™)Drug
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib (Tyverb™) and (Myocet™) | Experimental | Not described Receives: Drug: non-pegylated liposomal doxorubicon (Myocet™); Drug: Lapatinib (Tyverb™) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal dose for lapatinib plus myocet
Determination of the optimal dose for lapatinib plus Myocet™, in combination, in patients with HER2-positive metastatic breast cancer following disease progression during, or after, treatment with trastuzumab and taxanes as measured by MTD (Phase I)
Measured: 6 months
Secondary outcomes (1)
Overall survival
overall survival time (OS - time from registration to death from any cause) as assessed by standard RECIST criteria
Measured: From registration to death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2011 (estimated)
- Study startMar 2011
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Slower than anticipated accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Her2 Positive Metastatic Breast CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Trials Ireland
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01495884
- Sponsor's protocol ID
- ICORG 10-03
- Status last verified
- Oct 2015
- First submitted
- 16 Dec 2011
- Last updated
- 26 Oct 2015
- Results posted
- No
- Data monitoring committee
- No