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

Breast Cancer Clinical Trial

— CASA  

Official title:

Phase III Trial Evaluating the Role of Adjuvant Pegylated Liposomal Doxorubicin (PLD, Caelyx, Doxil) for Women (Age 66 Years or Older) With Endocrine Nonresponsive Breast Cancer Who Are Not Suitable for Being Offered a " Standard Chemotherapy Regimen"

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00296010
• Other study ID #: CDR0000463710
• Secondary ID: IBCSG-32-05BIG-C
• Status: Terminated
• Phase: Phase 3
• Start date: August 2005
• Est. completion date: December 2011

Study information

• Verified date: February 2021
• Source: International Breast Cancer Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 66 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide
cyclophosphamide 50 mg/day orally continuously for 16 weeks
• methotrexate
methotrexate 2.5 mg twice a day orally on days 1 and 4 of every week for 16 weeks
• pegylated liposomal doxorubicin hydrochloride
Caelyx (R) (Doxil (R)) 20 mg/m2 iv x 8 doses (delivered every 2 weeks)

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy
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.

Locations

Country	Name	City	State
Australia	Frankston Hospital	Frankston	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Cancer Care Centre at Nepean Hospital	Kingswood	New South Wales
Belgium	Centre Hospitalier Etterbeek Ixelles	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	AZ Groeninge - Oncologisch Centrum	Kortrijk
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Hungary	National Institute of Oncology	Budapest
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Ospedale degli Infermi - ASL 12	Biella
Italy	Ospedale Civile Ramazzini	Carpi
Italy	Ospedale Civile S. Croce	Fano
Italy	European Institute of Oncology	Milano
Italy	Ospedale Civile Rimini	Rimini
Italy	Ospedale Sant' Eugenio	Rome
Italy	Centro Sociale Oncologico	Treste
Italy	Policlinico Universitario Udine	Udine
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
New Zealand	Auckland City Hospital	Auckland
Romania	Institutul Oncologic - Universitatea de Medicina	Cluj-Napoca
Slovenia	Institute of Oncology - Ljubljana	Ljubljana
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Skaraborgs Hospital	Skovde
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Inselspital Bern	Bern
Switzerland	Oncocare Sonnenhof-Klinik Engeriedspital	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun

Sponsors (1)

Lead Sponsor	Collaborator
International Breast Cancer Study Group

Countries where clinical trial is conducted

Australia,  Belgium,  Hungary,  Italy,  New Zealand,  Romania,  Slovenia,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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