Liposomal Doxorubicin and Docetaxel in HER2 Negative Metastatic Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer; Neoplasm Metastasis
• Interventions: Drug: Non pegylated liposomal doxorubicin and docetaxel

• Registration Number: NCT00377559
• Lead Sponsor: Catharina Ziekenhuis Eindhoven

Brief Summary

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.

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 Timeline

• Study Start: 2006-05
• Study First Submitted: 2006-09-15
• Study First Submitted QC: 2006-09-15
• Study First Posted: 2006-09-18
• Primary Completion: 2009-11
• Study Completion: 2011-07
• Status Verified: 2011-08
• Last Update Submitted: 2015-10-05
• Last Update Posted: 2015-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1.	Non pegylated liposomal doxorubicin and docetaxel	Myocet+docetaxel

Primary Outcome Measures

Name	Time	Method
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 LVEF of ≥ 10% to < 50% without signs or symptoms of CHF	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

Secondary Outcome Measures

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

Trial Locations

Locations (10)

Jeroen Bosch Ziekenhuis; 🇳🇱 's-Hertogenbosch, Netherlands

Wilhelmina Ziekenhuis; 🇳🇱 Assen, Netherlands

Catharina-Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Ikazia Ziekenhuis; 🇳🇱 Rotterdam, Netherlands

Sint Elisabeth Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Mesos Medisch Centrum; 🇳🇱 Utrecht, Netherlands

Maxima Medisch Centrum; 🇳🇱 Veldhoven, Netherlands

VieCuri MC; 🇳🇱 Venlo, Netherlands

Ziekenhuis Walcheren; 🇳🇱 Vlissingen, Netherlands

Streekziekenhuis Koningin Beatrix; 🇳🇱 Winterswijk, Netherlands