Clinical trial NCT00005980: Comparison of Two Regimens of Liposomal Doxorubicin in Treating Women With Metastatic Breast Cancer
Official title: A Randomized Phase II Study of Two Different Schedules of Caelyx in Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 116
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of liposomal doxorubicin is more effective for metastatic breast cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of two regimens of liposomal doxorubicin in treating women who have metastatic breast cancer.

Detailed description: OBJECTIVES:

* Determine the response rate in women with metastatic breast cancer treated with two different dose schedules of doxorubicin HCL liposome.
* Assess the side effects of these treatment regimens in this patient population.
* Determine the duration of response in these patients treated with these regimens.
* Assess the concentration of doxorubicin in tumor tissue in patients with easily accessible metastases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, performance status (0-1 vs 2), visceral disease (yes vs no), available lesions for biopsy (yes vs no), prior adjuvant anthracyclines (yes vs no), and prior chemotherapy for advanced disease (yes vs no). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive doxorubicin HCL liposome IV over 1 hour every 6 weeks.
* Arm II: Patients receive doxorubicin HCL liposome IV over 1 hour every 4 weeks. Treatment continues for at least 36 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 64-100 patients (32-50 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven progressive or recurrent metastatic breast cancer
* Bidimensionally measurable disease with at least one target lesion

  * If previously irradiated lesions:

    * No preirradiated only lesions
    * Clear progression prior to study
    * New lesions in a previously irradiated region allowed
* Refusal of or medical contraindication to standard anthracycline containing regimen
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age:

* Any age

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin normal
* Transaminases less than 2 times upper limit of normal

Renal:

* Creatinine normal

Cardiovascular:

* Left ventricular ejection fraction normal by echocardiography or MUGA scan
* No significant cardiac history including:

  * Clinically significant atrial or ventricular arrhythmias requiring treatment
  * Medically controlled congestive heart failure
  * Significant angina or clinically and/or electrocardiographically documented myocardial infarction within the past year
  * Clinically significant valvular disease

Other:

* No other prior or concurrent malignancy within the past 5 years except contralateral breast cancer, or adequately treated basal cell skin cancer or carcinoma in situ of the cervix
* No psychological, familial, sociological, or geographical condition that would preclude study
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* See Disease Characteristics
* Prior adjuvant chemotherapy allowed if total doxorubicin dose is no greater than 300 mg/m2, total epirubicin dose is no greater than 450 mg/m\^2, and total mitoxantrone dose is no greater than 75 mg/m\^2
* No greater than one regimen of prior chemotherapy for metastatic disease
* No prior anthracyclines for metastatic disease
* No other concurrent cytotoxic therapy

Endocrine therapy:

* No concurrent hormonal therapy
* At least 4 weeks since prior progestins, estrogens, or androgens

Radiotherapy:

* See Disease Characteristics
* Concurrent palliative radiotherapy allowed if sole target lesion is outside irradiated field

Surgery:

* Not specified

Other:

* Concurrent bisphosphonates for metastatic bone disease and hypercalcemia secondary to malignancy allowed if bony lesions not only target lesion
* No other concurrent investigational therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Ludwig Boltzmann - Institute for Applied Cancer Research
city: Bordeaux
country: France
facility: Institut Bergonie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Paris
country: France
facility: Institut Curie - Section Medicale
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Ioannina
country: Greece
facility: University of Ioannina
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus
city: Milano (Milan)
country: Italy
facility: Mario Negri Institute for Pharmacological Research
city: Rome
country: Italy
facility: Istituti Fisioterapici Ospitalieri - Roma
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Genolier
country: Switzerland
facility: Clinique De Genolier
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: England
Study officials:
affiliation: Cancer Research Centre at Weston Park Hospital
name: Robert E. Coleman, MD, FRCP
role: STUDY_CHAIR
affiliation: Mario Negri Institute for Pharmacological Research
name: Maurizio D'Incalci, MD
role: STUDY_CHAIR
affiliation: Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
name: Christian Dittrich, MD
role: STUDY_CHAIR
References:
citation: Biganzoli L, Coleman R, Minisini A, Hamilton A, Aapro M, Therasse P, Mottino G, Bogaerts J, Piccart M. A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer. Crit Rev Oncol Hematol. 2007 Jan;61(1):84-9. doi: 10.1016/j.critrevonc.2006.07.008. Epub 2006 Nov 20.
citation: Coleman RE, Biganzoli L, Canney P, Dirix L, Mauriac L, Chollet P, Batter V, Ngalula-Kabanga E, Dittrich C, Piccart M. A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer. 2006 May;42(7):882-7. doi: 10.1016/j.ejca.2005.12.011. Epub 2006 Mar 7.