Liposomal Doxorubicin and Docetaxel in HER2 Negative Metastatic Breast Cancer (MYOTAX)

Phase II Multicentre Open Label Trial Evaluating the Efficacy and Safety of the Liposomal Doxorubicin (Myocet®) and Docetaxel (Taxotere®) Combination as First-line Treatment of Patients With Metastatic HER2/Neu Negative Breast Cancer

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Neoplasm Metastasis
• Intervention / Treatment: Drug: Non pegylated liposomal doxorubicin and docetaxel

Detailed Description

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

Myocet and Taxotere will be given for a maximum of 6 cycles. Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • 's-Hertogenbosch, Netherlands, 5211 NL
    • Jeroen Bosch Ziekenhuis
  • Assen, Netherlands, 9400 RA
    • Wilhelmina Ziekenhuis
  • Eindhoven, Netherlands, 5602 ZA
    • Catharina-ziekenhuis
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
  • Tilburg, Netherlands, 5000 LC
    • Sint Elisabeth Ziekenhuis
  • Utrecht, Netherlands, 3527 CE
    • Mesos Medisch Centrum
  • Veldhoven, Netherlands, 5500 MB
    • Maxima Medisch Centrum
  • Venlo, Netherlands, 5900 BX
    • VieCuri MC
  • Vlissingen, Netherlands, 4380 DD
    • Ziekenhuis Walcheren
  • Winterswijk, Netherlands, 7100 GG
    • Streekziekenhuis Koningin Beatrix

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women with histologically documented metastatic or locally advanced metastatic HER2/neu negative breast cancer.
• 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 ≤ 360 mg/m2 of doxorubicin or 600 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.; Myocet+docetaxel	Drug: Non pegylated liposomal doxorubicin and docetaxel; max. 6 courses; Other Names: Myocet, Taxotere

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classification	treatment period
Response rate	treatment period
Median time to progression	treatment period
Progression free survival	treatment period

Collaborators and Investigators

• Sponsor: Catharina Ziekenhuis Eindhoven
• Collaborators: Sanofi; Cephalon
• Investigators: Principal Investigator: Laurence J. van Warmerdam, MD, PhD, Catharina Ziekenhuis

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: September 15, 2006
• First Submitted That Met QC Criteria: September 15, 2006
• First Posted (Estimate): September 18, 2006

Study Record Updates

• Last Update Posted (Estimate): October 6, 2015
• Last Update Submitted That Met QC Criteria: October 5, 2015
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Breast cancer; cardiotoxicity; metastatic; docetaxel; liposomal; doxorubicin; HER2/neu negative metastatic breast cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: MYOTAX