Liposomal Doxorubicin Compared With Observation or Cyclophosphamide and Methotrexate in Treating Older Women Who Have Undergone Surgery for Breast Cancer

Phase 3

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: cyclophosphamide; Drug: methotrexate; Radiation: radiation therapy; Procedure: adjuvant therapy

• Registration Number: NCT00296010
• Lead Sponsor: ETOP IBCSG Partners Foundation

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate, cyclophosphamide, and liposomal doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving liposomal doxorubicin after surgery is more effective than observation or cyclophosphamide and methotrexate in treating breast cancer.

PURPOSE: This randomized phase III trial is studying liposomal doxorubicin to see how well it works compared with observation or cyclophosphamide and methotrexate in treating older women who have undergone surgery for breast cancer.

Detailed Description

OBJECTIVES:

Primary

* Compare the breast cancer-free interval in elderly women with resectable, hormone receptor-negative breast cancer treated with pegylated doxorubicin hydrochloride liposome (PDL) vs observation or PDL vs cyclophosphamide and methotrexate.

Secondary

* Compare the tolerability of these regimens in these patients.

* Compare the safety and toxic effects of these regimens in these patients.

* Compare the overall and progression-free survival of patients treated with these regimens.

* Compare the quality of life of patients treated with these regimens.

* Compare the sites of failure in patients treated with these regimens.

* Compare the competing causes of death in patients treated with these regimens.

* Compare the rate of second non-breast malignancy in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are assigned, based on patient preference, to 1 of 2 treatment groups.

* Group 1: Patients are randomized to 1 of 2 arms (arms I and II).

* Arm I: Patients receive pegylated doxorubicin hydrochloride liposome (PDL) IV over 1 hour on day 1. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients undergo observation only.

* Group 2: Patients are randomized to 1 of 2 treatment arms (arms III and IV).

* Arm III: Patients receive PDL as in arm I.

* Arm IV: Patients receive oral cyclophosphamide once daily on days 1-7 and oral methotrexate twice daily on days 1 and 4. Treatment repeats every week for 16 courses in the absence of disease progression or unacceptable toxicity.

All patients may undergo radiotherapy according to institutional standards either during surgery or after the completion of chemotherapy.

Quality of life is assessed at baseline and at 3, 6, and 12 months.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 1,296 patients will be accrued for this study.

Study Timeline

• Study Start: 2005-08
• Study First Submitted: 2006-02-23
• Study First Submitted QC: 2006-02-23
• Study First Posted: 2006-02-24
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-22
• Last Update Posted: 2021-02-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 77

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CASA-CM PLD	radiation therapy	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-CM CM	adjuvant therapy	Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks
CASA-Nil	radiation therapy	No adjuvant therapy
CASA-CM PLD	pegylated liposomal doxorubicin hydrochloride	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-CM PLD	adjuvant therapy	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-nil PLD	pegylated liposomal doxorubicin hydrochloride	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-nil PLD	adjuvant therapy	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-nil PLD	radiation therapy	Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks
CASA-CM CM	radiation therapy	Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks
CASA-CM CM	cyclophosphamide	Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks
CASA-CM CM	methotrexate	Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks

Primary Outcome Measures

Name	Time	Method
Breast cancer free interval by physical examination, laboratory tests, and investigations every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually as indicated after completion of study treatment	5 years after recruitment starts

Secondary Outcome Measures

Name	Time	Method
Adverse events assessed by CTCAE v3.0 every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually after completion of study treatment	5 years after recruitment starts
Quality of life assessed by Casa QL form, Mini-Cog, and VES-13 at baseline and at 2, 6, and 12 months after completion of study treatment	5 years after recruitment starts
Disease-free survival by physical examination, laboratory tests, and investigations every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually as indicated after completion of study treatment	5 years after recruitment starts
Overall survival by physical examination, laboratory tests, and investigations every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually as indicated after completion of study treatment	5 years after recruitment starts
Sites of failure by physical examination, laboratory tests, and investigations every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually as indicated after completion of study treatment	5 years after recruitment starts
Second (non-breast) malignancy by physical examination, laboratory tests, and investigations every 2 weeks for 16 weeks during treatment, every 3-6 months for 5 years, then annually as indicated after completion of study treatment	5 years after recruitment starts
Causes of death prior to breast cancer recurrence by physical examination, laboratory tests, and investigations every 2 wks for 16 wks during treatment, every 3-6 mo. for 5 yrs, then annually as indicated after completion of study treatment	5 years after recruitment starts

Trial Locations

Locations (33)

Centre Hospitalier Etterbeek Ixelles; 🇧🇪 Brussels, Belgium

AZ Groeninge - Oncologisch Centrum; 🇧🇪 Kortrijk, Belgium

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Nepean Cancer Care Centre at Nepean Hospital; 🇦🇺 Kingswood, New South Wales, Australia

Institutul Oncologic - Universitatea de Medicina; 🇷🇴 Cluj-Napoca, Romania

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Kantonsspital Graubuenden; 🇨🇭 Chur, Switzerland

Regionalspital; 🇨🇭 Thun, Switzerland

Gosford Hospital; 🇦🇺 Gosford, New South Wales, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Frankston Hospital; 🇦🇺 Frankston, Victoria, Australia

U.Z. Gasthuisberg; 🇧🇪 Leuven, Belgium

CHU Liege - Domaine Universitaire du Sart Tilman; 🇧🇪 Liege, Belgium

Centro di Riferimento Oncologico - Aviano; 🇮🇹 Aviano, Italy

Ospedale degli Infermi - ASL 12; 🇮🇹 Biella, Italy

National Institute of Oncology; 🇭🇺 Budapest, Hungary

Ospedali Riuniti di Bergamo; 🇮🇹 Bergamo, Italy

Ospedale Civile Ramazzini; 🇮🇹 Carpi, Italy

European Institute of Oncology; 🇮🇹 Milano, Italy

Ospedale Civile Rimini; 🇮🇹 Rimini, Italy

Ospedale Sant' Eugenio; 🇮🇹 Rome, Italy

Ospedale Civile S. Croce; 🇮🇹 Fano, Italy

Centro Sociale Oncologico; 🇮🇹 Treste, Italy

Policlinico Universitario Udine; 🇮🇹 Udine, Italy

Ospedale di Circolo e Fondazione Macchi; 🇮🇹 Varese, Italy

Institute of Oncology - Ljubljana; 🇸🇮 Ljubljana, Slovenia

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Skaraborgs Hospital; 🇸🇪 Skovde, Sweden

Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden

Inselspital Bern; 🇨🇭 Bern, Switzerland

Kantonspital Aarau; 🇨🇭 Aarau, Switzerland

Ospedale Beata Vergine; 🇨🇭 Mendrisio, Switzerland

Oncocare Sonnenhof-Klinik Engeriedspital; 🇨🇭 Bern, Switzerland