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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00296010




Registration number
NCT00296010
Ethics application status
Date submitted
23/02/2006
Date registered
24/02/2006
Date last updated
23/02/2021

Titles & IDs
Public title
Liposomal Doxorubicin Compared With Observation or Cyclophosphamide and Methotrexate in Treating Older Women Who Have Undergone Surgery for Breast Cancer
Scientific 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"
Secondary ID [1] 0 0
IBCSG-32-05
Secondary ID [2] 0 0
CDR0000463710
Universal Trial Number (UTN)
Trial acronym
CASA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - methotrexate
Treatment: Drugs - pegylated liposomal doxorubicin hydrochloride
Treatment: Surgery - adjuvant therapy
Treatment: Other - radiation therapy

Experimental: CASA-nil PLD - Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks

Active Comparator: CASA-Nil - No adjuvant therapy

Experimental: CASA-CM PLD - Adjuvant pegylated liposomal doxorubicin (PLD) for 16 weeks

Active Comparator: CASA-CM CM - Low-dose, metronomic cyclophosphamide and methotrexate (CM) for 16 weeks


Treatment: Drugs: cyclophosphamide
cyclophosphamide 50 mg/day orally continuously for 16 weeks

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

Treatment: Drugs: pegylated liposomal doxorubicin hydrochloride
Caelyx (R) (Doxil (R)) 20 mg/m2 iv x 8 doses (delivered every 2 weeks)

Treatment: Surgery: adjuvant therapy


Treatment: Other: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
5 years after recruitment starts
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
5 years after recruitment starts
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
5 years after recruitment starts
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
5 years after recruitment starts
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
5 years after recruitment starts
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
5 years after recruitment starts
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
5 years after recruitment starts
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
5 years after recruitment starts

Eligibility
Key inclusion criteria
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
Minimum age
66 Years
Maximum age
120 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
77
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
Gosford Hospital - Gosford
Recruitment hospital [2] 0 0
Nepean Cancer Care Centre at Nepean Hospital - Kingswood
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
Frankston Hospital - Frankston
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Kortrijk
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Liege
Country [5] 0 0
Hungary
State/province [5] 0 0
Budapest
Country [6] 0 0
Italy
State/province [6] 0 0
Aviano
Country [7] 0 0
Italy
State/province [7] 0 0
Bergamo
Country [8] 0 0
Italy
State/province [8] 0 0
Biella
Country [9] 0 0
Italy
State/province [9] 0 0
Carpi
Country [10] 0 0
Italy
State/province [10] 0 0
Fano
Country [11] 0 0
Italy
State/province [11] 0 0
Milano
Country [12] 0 0
Italy
State/province [12] 0 0
Rimini
Country [13] 0 0
Italy
State/province [13] 0 0
Rome
Country [14] 0 0
Italy
State/province [14] 0 0
Treste
Country [15] 0 0
Italy
State/province [15] 0 0
Udine
Country [16] 0 0
Italy
State/province [16] 0 0
Varese
Country [17] 0 0
New Zealand
State/province [17] 0 0
Auckland
Country [18] 0 0
Romania
State/province [18] 0 0
Cluj-Napoca
Country [19] 0 0
Slovenia
State/province [19] 0 0
Ljubljana
Country [20] 0 0
Sweden
State/province [20] 0 0
Gothenburg
Country [21] 0 0
Sweden
State/province [21] 0 0
Skovde
Country [22] 0 0
Switzerland
State/province [22] 0 0
Aarau
Country [23] 0 0
Switzerland
State/province [23] 0 0
Bern
Country [24] 0 0
Switzerland
State/province [24] 0 0
Chur
Country [25] 0 0
Switzerland
State/province [25] 0 0
Mendrisio
Country [26] 0 0
Switzerland
State/province [26] 0 0
St. Gallen
Country [27] 0 0
Switzerland
State/province [27] 0 0
Thun

Funding & Sponsors
Primary sponsor type
Other
Name
ETOP IBCSG Partners Foundation
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00296010
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Diana Crivellari, MD
Address 0 0
Centro di Riferimento Oncologico, Aviano (Italy)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00296010