Clinical trial NCT00377559: Liposomal Doxorubicin and Docetaxel in HER2 Negative Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Neoplasm Metastasis
Keywords: Breast cancer
metastatic
cardiotoxicity
liposomal
doxorubicin
docetaxel
HER2/neu negative metastatic breast cancer
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
Collaborators: name: Cephalon
name: Sanofi
First posted: 2006-09-18
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiotoxicity (definite or probable cardiac death)
timeFrame: treatment period
measure: Signs or symptoms of congestive heart failure (CHF), New York Heart Association (NYHA) class III-IV
timeFrame: treatment period
measure: Decline in left ventricular ejection fraction (LVEF) of ≥ 5% to < 50% with mild signs or symptoms of CHF (NYHA class < III)
timeFrame: treatment period
measure: Decline in LVEF of ≥ 10% to < 50% without signs or symptoms of CHF
timeFrame: treatment period
Secondary outcomes:
measure: Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classification
timeFrame: treatment period
measure: Response rate
timeFrame: treatment period
measure: Median time to progression
timeFrame: treatment period
measure: Progression free survival
timeFrame: treatment period
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Assen
country: Netherlands
facility: Wilhelmina Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina-Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Tilburg
country: Netherlands
facility: Sint Elisabeth Ziekenhuis
city: Utrecht
country: Netherlands
facility: Mesos Medisch Centrum
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Venlo
country: Netherlands
facility: VieCuri MC
city: Vlissingen
country: Netherlands
facility: Ziekenhuis Walcheren
city: Winterswijk
country: Netherlands
facility: Streekziekenhuis Koningin Beatrix
Study officials:
affiliation: Catharina Ziekenhuis
name: Laurence J. van Warmerdam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: