The Myocet/Lapatinib Study. ICORG 10-03, V5

This study is currently recruiting participants.
Verified January 2014 by ICORG- All Ireland Cooperative Oncology Research Group
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01495884
First received: December 16, 2011
Last updated: January 22, 2014
Last verified: January 2014

December 16, 2011
January 22, 2014
March 2011
May 2014   (final data collection date for primary outcome measure)
Optimal dose for lapatinib plus myocet [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
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)
Same as current
Complete list of historical versions of study NCT01495884 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: From registration to death ] [ Designated as safety issue: No ]
overall survival time (OS - time from registration to death from any cause) as assessed by standard RECIST criteria
Overall survival outcome [ Designated as safety issue: No ]
overall survival time (OS - time from registration to death from any cause) as assessed by standard RECIST criteria
Not Provided
Not Provided
 
The Myocet/Lapatinib Study. ICORG 10-03, V5
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.

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).

Primary Objective:

  1. 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).
  2. 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:

  1. 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).
  2. To assess the safety and tolerability of this regimen in these patients.
  3. To assess the incidence of cardiotoxicity in these patients treated with this regimen.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Her2 Positive Metastatic Breast Cancer
  • Drug: non-pegylated liposomal doxorubicon (Myocet™)
  • Drug: Lapatinib (Tyverb™)
Experimental: Lapatinib (Tyverb™) and (Myocet™)
Interventions:
  • Drug: non-pegylated liposomal doxorubicon (Myocet™)
  • Drug: Lapatinib (Tyverb™)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
21
October 2016
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written informed consent obtained prior to any study-related procedures.
  2. 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.
  3. Histologically confirmed metastatic breast cancer
  4. Documented HER2 overexpression (IHC 3+ or FISH or CISH positive)
  5. At least one measurable lesion according to RECIST criteria. Patients with bone only disease are not eligible.
  6. Patients with controlled brain metastasis are eligible.
  7. 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
  8. Prior treatment must have contained trastuzumab and taxane. Patients may have been treated with Lapatinib previously.
  9. Life expectancy of at least 12 weeks
  10. ECOG Performance Status of ≤ 2
  11. 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
  12. 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
  13. Patients must have recovered from clinically significant side effects associated with prior radiotherapy and chemotherapy
  14. Able to swallow and retain oral medication.
  15. 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:

Exclusion Criteria:

  1. Pregnant or lactating women
  2. Prior anthracycline chemotherapy with a lifetime dose exceeding 360 mg/m2 doxorubicin or 550 mg/m2 epirubicin
  3. Documented history of poorly controlled hypertension), arrhythmia, clinically significant valvular disease, angina requiring treatment, transmural infarction, myocardial infarction within the previous 6 months
  4. 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
  5. Dementia, altered mental status, or any other psychiatric condition that would interfere with the patient's safety or informed consent
  6. Active or uncontrolled bacterial, viral or fungal infection.
  7. 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
  8. Concurrent cancer therapy (chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or within 4 weeks preceding the first dose of investigational product)
  9. Unresolved or unstable, serious toxicity from prior administration of another investigational product
  10. Concurrent treatment with an investigational drug within 4 weeks preceding the first dose of investigational product
  11. Known hypersensitivity to lapatinib and Myocet™ or their excipients
  12. Any other contraindications for lapatinib and Myocet™
  13. 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.
Female
18 Years and older
No
Not Provided
Ireland
 
NCT01495884
ICORG 10-03
No
ICORG- All Ireland Cooperative Oncology Research Group
ICORG- All Ireland Cooperative Oncology Research Group
Not Provided
Not Provided
ICORG- All Ireland Cooperative Oncology Research Group
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP