Doxorubicin Hydrochloride Liposome as First-Line Therapy in Treating Older Women With Metastatic Breast Cancer

Multicenter Study of PEGylated Liposomal Doxorubicin in Geriatric Oncology - Metastatic Breast Cancer - First-line Treatment PEGylated Liposomal Doxorubicin in Patients Older Than 70 Years, Breast Cancer Metastasis

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well doxorubicin hydrochloride liposome works as first-line therapy in treating older women with metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin hydrochloride

Detailed Description

OBJECTIVES:

Primary

• Evaluate the effectiveness of pegylated liposomal doxorubicin hydrochloride, in terms of objective response rate, in elderly women with metastatic breast cancer.

Secondary

• Determine the feasibility of this drug in these patients.
• Evaluate chemotherapy-induced toxicities in these patients.
• Assess the disease-free survival and overall survival of these patients.
• Study the geriatric covariates.
• Assess the covariates predictive of the hematopoietic reserve and the risk of febrile neutropenia in these patients.

OUTLINE: This is a multicenter study.

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60-90 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity or progressive disease.

After completion of study therapy, patients are followed up periodically for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75181
    • Hotel Dieu de Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive ductal or lobular adenocarcinoma of the breast

  • Metastatic disease as confirmed by ≥ 1 of the following:

    • Histology or cytology
    • Radiology
    • Elevated CA 15-3 levels
• No HER2/neu overexpression by IHC or FISH

• Measurable (≥ 10 mm) or evaluable disease

  • Bone lesions or isolated pleural effusion allowed
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Postmenopausal
• Life expectancy > 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Alkaline phosphatase ≤ 5 times ULN
• Bilirubin ≤ 2 times ULN
• Creatinine clearance ≥ 30 mL/min
• LVEF ≥ 50%
• No congestive heart failure or other uncontrolled cardiac disease
• No other malignancy within the past 5 years except for curatively treated carcinoma in situ of the cervix, urothelial in situ carcinoma, or basal cell cancer
• No prior hypersensitivity to anthracyclines
• No psychological, familial, social, or geographical reason that would preclude study follow-up
• No serious illness or physical or mental condition resulting in a permanent disability that may preclude successful treatment

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for metastatic disease

• Prior adjuvant chemotherapy allowed

  • No development of metastatic disease within 6 months after completion of adjuvant anthracycline-based chemotherapy
• No more than 300 mg/m² of prior doxorubicin hydrochloride or 600 mg/m² of prior epirubicin hydrochloride in the adjuvant setting
• More than 30 days since prior participation in another clinical trial

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: single arm	Drug: pegylated liposomal doxorubicin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	3 and 6 cures

Collaborators and Investigators

• Sponsor: ARCAGY/ GINECO GROUP
• Investigators: Principal Investigator: Laure Chauvenet, MD, Hotel Dieu de Paris

Publications and helpful links

General Publications

• Falandry C, Brain E, Bonnefoy M, Mefti F, Jovenin N, Rigal O, Guillem O, El Kouri C, Uwer L, Abadie-Lacourtoisie S, Cretin J, Jacquin JP, Paraiso D, Freyer G. Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial. Eur J Cancer. 2013 Sep;49(13):2806-14. doi: 10.1016/j.ejca.2013.04.027. Epub 2013 Jun 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: August 14, 2009
• First Submitted That Met QC Criteria: August 14, 2009
• First Posted (Estimate): August 17, 2009

Study Record Updates

• Last Update Posted (Estimate): October 29, 2014
• Last Update Submitted That Met QC Criteria: October 28, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; invasive ductal breast carcinoma; invasive lobular breast carcinoma; HER2-negative breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CDR0000633600; ARCAGY-DOGMES; ARCAGY-GINECO-BR106; INCA-RECF0511; EUDRACT-2007-002736-28; SCHER-ARCAGY-DOGMES