Liposomal Doxorubicin, Trastuzumab, and Docetaxel in HER2 Positive Metastatic Breast Cancer (MYOHERTAX)

• ClinicalTrials.gov Identifier: NCT00377780
• Recruitment Status: Terminated
• First Posted: September 18, 2006
• Last Update Posted: September 23, 2015
• Sponsor: Laurence J.C. van Warmerdam
• Collaborators: Cephalon; Sanofi
• Information provided by (Responsible Party): Laurence J.C. van Warmerdam, Catharina Ziekenhuis Eindhoven

Study Description

Brief Summary:

This is an open phase II study evaluating the efficacy and safety of the non pegylated liposomal doxorubicin (Myocet®), trastuzumab (Herceptin®), and docetaxel (Taxotere®) combination as first-line treatment of patients with metastatic HER2/neu positive breast cancer.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Neoplasm Metastasis	Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel	Phase 2

Detailed Description:

Phase II non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic HER2/neu positive breast cancer not yet treated with chemotherapy for metastatic disease.

Myocet and Taxotere will be given for a maximum of 6 cycles, Herceptin treatment for 1 year is recommended.

Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Multicentre Open Label Study Evaluating the Efficacy and Safety of Liposomal Doxorubicin, Trastuzumab, Docetaxel as First-line Treatment of Patients With HER2 Positive Metastatic Breast Cancer
• Study Start Date: August 2006
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Myocet + docetaxel + trastuzumab	Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel; max. 6 courses; Other Name: Myocet, herceptin, toxotere

Outcome Measures

Primary Outcome Measures :

1. Cardiotoxicity (definite or probable cardiac death) [ Time Frame: treatment period ]
2. Signs or symptoms of congestive heart failure (CHF), New York Heart Association (NYHA) class III-IV [ Time Frame: treatment period ]
3. Decline in left ventricular ejection fraction (LVEF) of ≥ 5% to < 50% with mild signs or symptoms of CHF (NYHA class < III) [ Time Frame: treatment period ]
4. Decline in LVEF of ≥ 10% to < 50% without signs or symptoms of CHF [ Time Frame: treatment period ]

Secondary Outcome Measures :

1. Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classification [ Time Frame: treatment period ]
2. Response rate [ Time Frame: treatment period ]
3. Median time to progression [ Time Frame: treatment period ]
4. Progression free survival [ Time Frame: treatment period ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Women with histologically documented metastatic or locally advanced metastatic HER2/neu positive breast cancer at 1st line of palliative chemotherapy.
• In the case of previous adjuvant or neoadjuvant chemotherapy with anthracyclines or taxanes, this must have been completed more than 12 months before inclusion.
• In the case of previous adjuvant or neoadjuvant chemotherapy, cumulative anthracycline dose ≤ 240 mg/m2 of doxorubicin or 450 mg/m2 of epirubicin or 75 mg/m2 of mitoxantrone on inclusion.
• Previous endocrine therapy is authorized (endocrine therapy other than goserelin must be stopped before starting treatment).
• Previous radiotherapy is authorized, if discontinued ≥ 4 weeks prior to inclusion in the study and if < 10% of the bone marrow was within the irradiated area.
• Age ≥ 18 years.
• Performance status 0,1, or 2.
• Life expectancy ≥ 3 months.
• Evaluable disease.
• Normal LVEF (multigated acquisition [MUGA] scan or echocardiography).
• Normal haematological, hepatic and renal parameters: neutrophils ≥ 1.5 x 10^9/l; platelets ≥ 100 x 10^9/l; hemoglobin (Hb) ≥ 6 mmol/L; total bilirubin ≤ 1.5 times the upper limit of normal (ULN); transaminases ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 x ULN; creatinine ≤ 1.5 x ULN.
• Dated and signed written informed consent.

Exclusion Criteria:

• Previous chemotherapy for metastatic disease.
• History of other cancer, except for cervical carcinoma in situ treated by cone resection or basal cell or squamous cell skin cancer.
• History of congestive heart failure or myocardial infarction ≤ 1 year; cardiac function: NYHA ≥ 2 or LVEF < 50%.
• Uncontrolled significant heart disease, such as unstable angina.
• Poorly controlled hypertension.
• Performance status 3, 4.
• Symptomatic or progressive brain metastases.
• Active infection or other serious underlying disease.
• Concomitant participation in other clinical trials.
• Pregnant women or nursing mothers; patients of childbearing potential without effective contraception.
• Absolute medical contraindication to the use of corticosteroid premedication.
• Allergy to polysorbate 80, doxorubicin, or egg lecithin.
• NCI-CTC grade > 1 peripheral neuropathy.
• Patients not able to comply with regular medical follow-up

Contacts and Locations

Locations

Netherlands

Ziekenhuis Rijnstate

Arnhem, Netherlands, 6800 TA

Wilhelmina Ziekenhuis

Assen, Netherlands, 9400 RA

Catharina-Ziekenhuis

Eindhoven, Netherlands, 5602 ZA

Ikazia Ziekenhuis

Rotterdam, Netherlands, 3083 AN

Maxima Medisch Centrum

Veldhoven, Netherlands, 5500 MB

VieCuri MC

Venlo, Netherlands, 5900 BX

Streekziekenhuis Koningin Beatrix

Winterswijk, Netherlands, 7100 GG

Sponsors and Collaborators

Laurence J.C. van Warmerdam

Cephalon

Sanofi

Investigators

• Principal Investigator: Laurence J. van Warmerdam, MD, PhD; Catharina Ziekenhuis Eindhoven

More Information

• Responsible Party: Laurence J.C. van Warmerdam, internist, Catharina Ziekenhuis Eindhoven
• ClinicalTrials.gov Identifier: NCT00377780
• Other Study ID Numbers: MYOHERTAX
• First Posted: September 18, 2006
• Last Update Posted: September 23, 2015
• Last Verified: September 2015

Keywords provided by Laurence J.C. van Warmerdam, Catharina Ziekenhuis Eindhoven:

Breast cancer; metastatic; cardiotoxicity; liposomal; doxorubicin; trastuzumab; docetaxel; HER2/neu positive metastatic breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasm Metastasis; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Neoplastic Processes; Pathologic Processes; Docetaxel; Doxorubicin; Liposomal doxorubicin; Trastuzumab; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antineoplastic Agents, Immunological