PRIMARY ENDPOINT

• Breast cancer-free interval (events are reappearance of invasive breast cancer at any site, including contralateral disease)

SECONDARY ENDPOINTS

• Tolerability (treatment completion) • Adverse events• Quality of life*• Disease-free survival (includes second malignancies and deaths)• Sites of failure• Second (non-breast) malignancy• Overall survival• Competing causes of death

SAMPLE SIZE / STATISTICS

• Trial designed to have 80% power to detect a 30% reduction in the risk of a breast cancer event (hazard ratio = 0.70; an improvement in 5-year BCFI from 65% without PLD to 74% with PLD) using a two-sided 0.05 level test of significance.

• Total sample size required = 1,296 patients to achieve goal of 258 breast cancer events.

* For non-IBCSG Centers, extent of participation in the quality of life study is to be determined at the activation of the trial for each cooperative group.

INTERNATIONAL BREAST CANCER STUDY GROUP

IBCSG 32-05/BIG 1-05

Chemotherapy Adjuvant Study for Women at advanced Age (CASA)

Phase III trial evaluating the role of adjuvant pegylated liposomal doxorubicin (PLD, CaelyxTM, Doxil®)

for women (age 66 years or older) with endocrine nonresponsive breast cancer who are not suitable for

being offered a “standard chemotherapy regimen”

STUDY CHAIRS Dr. Diana Crivellari, Aviano, Italy — dcrivellari@cro.it

Dr. Silvia Dellapasqua, Milan, Italy —silvia.dellapasqua@ibcsg.org

Dr. Anne Hamilton, Camperdown, Australia—anne.hamilton@cs.nsw.gov.au

I B C S G

BIG

REPORTING SAEs:

The investigator/MD responsible for the patient must fax a signed Serious Adverse Event Form 32-SAE-A in English within 24 hours to the DataFax data submission fax number for the participating center.

CONTACT INFORMATION:International Breast Cancer Study Group

IBCSG Coordinating Center Effingerstrasse 40 CH - 3008 Berne www.ibcsg.org

e-mail: ibcsgcc@ibcsg.org CASA e-mail: ibcsg32-05_casa@ibcsg.org

For patients who, according to the treating physician and/or to the patient’s preferences, are candidates to receive no adjuvant therapy

PLD 20 mg/m2 IV q 2 wk x 8

No adjuvant therapy (nil)

Option 1: CASA–nil

R

For patients who, according to the treating physician and/or to the patient’s preferences, are candidates to receive some adjuvant therapy

Option 2: CASA–CM

PLD 20 mg/m2 IV q 2 wk x 8

Low-dose, metronomic CM

R

All regimens are 16 weeks duration. C = cyclophosphamide 50 mg PO q d x 16 wk;

M = methotrexate 2.5 mg PO bid d 1 & 4 q wk x 16 wk.

IBCSG 32-05/BIG 1-05 STUDY DESIGN

• Randomization and start of chemotherapy should take place as soon as possible following surgery, but no later than 16 weeks

POPULATION

Older postmenopausal women (66 years of age or older)• Histologically proven, completely resected, early-stage breast cancer• Endocrine-nonresponsive breast cancer• Patients must not be candidates for endocrine therapy or for an adjuvant chemotherapy program which includes a “standard” anthracycline-containing chemotherapy regimen• Patients must have quality of life, functional (VES-13), and cognitive (Mini-Cog) geriatric assessments prior to randomization