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

Her2 Positive Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01495884
• Other study ID #: ICORG 10-03
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: December 16, 2011
• Last updated: October 23, 2015
• Start date: March 2011
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: ICORG- All Ireland Cooperative Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland:Irish Medicines Board (IMB)
• Study type: Interventional

Clinical 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 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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Her2 Positive Metastatic Breast Cancer

Intervention

Drug:
• non-pegylated liposomal doxorubicon (Myocet™)

• Lapatinib (Tyverb™)

Locations

Country	Name	City	State
Ireland	Bon Secours Hospital	Cork
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misercordiae University Hospital	Dublin
Ireland	Mater Private Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	University Hospital Limerick	Limerick
Ireland	Waterford Regional Hospital	Waterford

Sponsors (1)

Lead Sponsor	Collaborator
ICORG- All Ireland Cooperative Oncology Research Group

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	6 months	Yes
Secondary	Overall survival	overall survival time (OS - time from registration to death from any cause) as assessed by standard RECIST criteria	From registration to death	No