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

NCT00296010 | Terminated Phase 3 DMC

• 6 other identifiers: CDR0000463710IBCSG-32-05BIG-CASA2005-003434-18BIG-1-05EU-205112
• Study Type: interventional
• Target: 77
• Locations: 9 countries
• Sites: 33

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.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (4)

CASA-nil PLD

EXPERIMENTAL

Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks

Drug: pegylated liposomal doxorubicin hydrochloride; Procedure: adjuvant therapy; Radiation: radiation therapy

CASA-Nil

ACTIVE COMPARATOR

No adjuvant therapy

Radiation: radiation therapy

CASA-CM PLD

EXPERIMENTAL

Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks

Drug: pegylated liposomal doxorubicin hydrochloride; Procedure: adjuvant therapy; Radiation: radiation therapy

CASA-CM CM

ACTIVE COMPARATOR

Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks

Drug: cyclophosphamide; Drug: methotrexate; Procedure: adjuvant therapy; Radiation: radiation therapy

Interventions

cyclophosphamide DRUG

cyclophosphamide 50 mg/day orally continuously for 16 weeks

CASA-CM CM

methotrexate DRUG

methotrexate 2.5 mg twice a day orally on days 1 and 4 of every week for 16 weeks

CASA-CM CM

pegylated liposomal doxorubicin hydrochloride DRUG

Caelyx (R) (Doxil (R)) 20 mg/m2 iv x 8 doses (delivered every 2 weeks)

CASA-CM PLD; CASA-nil PLD

adjuvant therapy PROCEDURE

CASA-CM CM; CASA-CM PLD; CASA-nil PLD

radiation therapy RADIATION

Radiation therapy should be used according to institutional accepted guidelines. Radiation therapy to the conserved breast is recommended. Radiation therapy to the chest wall following mastectomy is optional (if given, it may also include nodal fields). Radiation therapy may be given either during operation or after all chemotherapy.

CASA-CM CM; CASA-CM PLD; CASA-Nil; CASA-nil PLD

Eligibility Criteria

• Age: 66 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer * Disease must be confined to the breast and axillary nodes without detected masses elsewhere * No history of prior ipsilateral or contralateral invasive breast cancer * Resected disease * No more than 16 weeks since last surgery to remove the tumor * No known clinical residual locoregional disease * Margins must be negative for invasive breast cancer and ductal carcinoma in situ * No locally advanced, inoperable breast cancer including any of the following: * Inflammatory breast cancer * Supraclavicular node involvement * Enlarged internal mammary nodes unless pathologically negative * Synchronous bilateral invasive breast cancer (diagnosed in the past 2 months) allowed if all tumors are hormone receptor-negative * Must not be a candidate for endocrine therapy or standard chemotherapy * Hormone receptor-negative disease PATIENT CHARACTERISTICS: * Female * Menopausal status: postmenopausal * ECOG performance status 0-2 * Platelet count ≥ 100,000/mm\^3 * Granulocyte count ≥ 1,500/mm\^3 * WBC ≥ 3,000/mm\^3 * AST and ALT ≤ 1.5 times upper limit of normal (ULN) * Bilirubin normal * Creatinine clearance ≥ 50 mL/min * Creatinine \< 1.35 mg/dL * No significant malabsorption syndrome or disease affecting gastrointestinal tract function * No myocardial infarction within the past 6 months * No pulmonary embolism within the past 6 months * No deep vein thrombosis within the past 6 months * No New York Heart Association class III or IV heart disease * LVEF ≥ 50% by echocardiography, radionucleotide ventriculography, or MUGA * No evidence of acute ischemia by ECG * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or bladder, or ipsilateral or contralateral breast carcinoma in situ * No active, uncontrolled infection * No active hepatitis B or C virus infection * No other chronic infection * Patients must not have any of the following "geriatric syndromes": * Dementia * Delirium * Major depression (as diagnosed by a psychiatrist) * Recent falls * Spontaneous bone fractures * Neglect * Abuse * No evidence of medically relevant conduction system abnormalities that would preclude study entry * No other nonmalignant, uncontrolled systemic diseases, psychiatric illness, or addictive or cognitive disorder that would preclude study participation or compliance PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior raloxifene, tamoxifen citrate, or other selective estrogen receptor modulators (SERMs) * No concurrent recombinant human epoetin alfa or pegfilgrastim * No prior neoadjuvant or adjuvant therapy for breast cancer except radiotherapy * Concurrent trastuzumab (Herceptin®) allowed * No concurrent hormonal replacement therapy * No other concurrent hormonal therapy (including estrogen, progesterone, androgens, tamoxifen citrate, SERMs, or aromatase inhibitors) except for the following: * Steroids for adrenal failure * Hormones for non-disease-related conditions (e.g., insulin for diabetes) * Intermittent dexamethasone as an antiemetic * No other concurrent investigational agents * No concurrent bisphosphonates, except for the treatment of osteoporosis * For patients who received prior anthracyclines, the following criteria must be met: * Cumulative dose ≤ 240 mg/m² for conventional doxorubicin * ≤ 140 mg/m² in case of prior doxorubicin and left chest radiotherapy (LCRT) * Cumulative dose ≤ 400 mg/m² for epirubicin * ≤ 230 mg/m² in case of prior epirubicin and LCRT

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (33)

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Nepean Cancer Care Centre at Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Centre Hospitalier Etterbeek Ixelles

Brussels, B-1050, Belgium

Location

AZ Groeninge - Oncologisch Centrum

Kortrijk, 8500, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

Ospedale degli Infermi - ASL 12

Biella, 13900, Italy

Location

Ospedale Civile Ramazzini

Carpi, 41012, Italy

Location

Ospedale Civile S. Croce

Fano, 61032, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Ospedale Civile Rimini

Rimini, 47900, Italy

Location

Ospedale Sant' Eugenio

Rome, 00144, Italy

Location

Centro Sociale Oncologico

Treste, 34100, Italy

Location

Policlinico Universitario Udine

Udine, 33100, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Auckland City Hospital

Auckland, 1, New Zealand

Location

Institutul Oncologic - Universitatea de Medicina

Cluj-Napoca, 3400, Romania

Location

Institute of Oncology - Ljubljana

Ljubljana, Sl-1000, Slovenia

Location

Sahlgrenska University Hospital

Gothenburg, S-413 45, Sweden

Location

Skaraborgs Hospital

Skövde, 541 85, Sweden

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Oncocare Sonnenhof-Klinik Engeriedspital

Bern, CH-3012, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Methotrexate; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Diana Crivellari, MD

  Centro di Riferimento Oncologico, Aviano (Italy)

  STUDY CHAIR

• Silvia Dellapasqua, MD

  European Institute of Oncology, Milano (Italy)

  STUDY CHAIR

• Anne Hamilton, MD

  Royal Prince Alfred Hospital, Camperdown (Australia)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: August 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 23, 2021

Record last verified: 2021-02

Locations

BE (5); IT (11); SL (1); AU (4); RO (1); SE (2); HU (1); CH (7); NZ (1)