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” - Chemotherapy Adjuvant Study for women at advanced Age (CASA)

• Register: EUCTR
• Last refreshed on: 18 October 2021
• Main ID: EUCTR2005-003434-18-FR
• Date of registration: 26/03/2007
• Prospective Registration: Yes
• Primary sponsor: International Breast Cancer Study Group (IBCSG)
• Public 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” - Chemotherapy Adjuvant Study for women at advanced Age (CASA)
• 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” - Chemotherapy Adjuvant Study for women at advanced Age (CASA)
• Date of first enrolment: 21/09/2007
• Target sample size: 1296
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003434-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Nil (no adjuvant therapy)
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Hungary, Italy, Slovenia, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Patient Characteristics:
- Women aged 66 years or older with histologically proven, resected breast cancer.
- Patients must not be candidates for endocrine therapy or standard chemotherapy regimen.
- Performance status (ECOG) 0-2.

Disease Characteristics:
- Patients must have endocrine nonresponsive tumors. (The recommended definition of endocrine nonresponsive: ER less than 10% of cells stained positive by immunohistochemical evaluation. If PgR is done, it should also be less than 10% of cells stained positive by immunohistochemical evaluation.)
- The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere.
- Patients with synchronous (diagnosed histologically within 2 months) bilateral invasive breast cancer are eligible if all tumors are endocrine nonresponsive and other criteria in 3.2 and 3.3 are met.

Prior Surgery:
- Patients must have had surgery for primary breast cancer (with or without axillary
clearance) with no known clinical residual loco-regional disease.
- Margins must be negative for invasive breast cancer and DCIS.
- Patients should be randomized and start treatment as close to definitive surgery as
possible; within 6 weeks is recommended and not more than 16 weeks (from last surgery in case of bilateral breast cancer).

Prior Treatment:
- No prior neoadjuvant or adjuvant therapy for breast cancer. Note: Radiotherapy is allowed prior to randomization.
- Raloxifene, tamoxifen, or other SERM must be discontinued at least 4 weeks before
randomization.

Concurrent Treatment (at the time of randomization patients should not be
receiving these treatments):
- No hormone replacement therapy (HRT).
- No hormonal therapy, except steroids for adrenal failure, hormones for non-breast cancer related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic.
- No treatment with bisphosphonates, except for the treatment of osteoporosis.

Organ function at the time of randomization (within 2 months before
randomization):
- Adequate bone marrow, renal, and hepatic function must be assessed within 2 months before randomization and values must meet the following criteria:
• WBC = 3.0 G/L
• Granulocyte count = 1.500 G/L
• Platelet count = 100 G/L
• Serum creatinine < 120 µmol/L (< 1.35 mg/dl)
• Calculated creatinine clearance at least 50 mL/min
• Serum bilirubin within normal/reference range
• AST/ALT within 1.5 x upper normal limit
- Adequate cardiovascular function defined as the following must be assessed within 2 months before randomization:
• LVEF = 50% by echocardiography, radionuclide ventriculography or Multigated
Angiography (MUGA)
• No ECG evidence of acute ischemia
• No evidence of medically relevant conduction system abnormalities, which in the
opinion of the investigator would preclude trial entry
• No myocardial infarction within the past 6 months
• No New York Heart Association (NYHA) class III or IV congestive heart failure

Protocol Requirements BEFORE Randomization:
- Written Informed Consent (IC) must be signed and dated by the patient and the
investigator prior to completing QL Forms and prior to randomization.
- Patients must have completed the baseline QL assessment, including the patient-rated Quality of Life Quetionnaire Form QL as well as the two physician-documented tests for cognitive (Mini-Cog test) and physical (Vulnerable Elders Survey [VES-13] test) functioning and the Assessment Checklist. The only exceptions are physical impair
Exclusion criteria:
Disease Characteristics:
- Patients with locally advanced inoperable breast cancer including inflammatory breast cancer, supraclavicular node involvement, or enlarged internal mammary nodes (unless pathologically negative).

Prior/Concurrent Disease:
- Patients with a history of any prior ipsilateral or contralateral invasive breast cancer.
- Patients with previous or concomitant malignancy diagnosed within the past five years. Patients with adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, contra- or ipsilateral in situ breast carcinoma are eligible regardless of the date of diagnosis.
- Patients with other non-malignant uncontrolled systemic diseases that would
preclude trial entry in the opinion of the investigator. Specifically not eligible are patients with uncontrolled active infection, chronic infection such as active HBV or HCV.
- Patients with myocardial infarction, pulmonary embolism or deep venous thrombosis within 6 months prior to randomization.
- Patients with significant malabsorption syndrome or disease affecting gastrointestinal tract function.
- Patients with at least one of the so-called “geriatric syndromes”: dementia, delirium, major depression (as diagnosed by a psychiatrist), recent falls, spontaneous bone fractures, neglect, and abuse.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Older women (66 years of age or older) with histologically proven, resected breast cancer. The disease must be classified as endocrine nonresponsive and patients must not be candidates for endocrine therapy or for an adjuvant chemotherapy program which includes a “standard” anthracycline-containing chemotherapy regimen.
MedDRA version: 8.1 Level: LLT Classification code 10006188 Term: Breast cancer female NOS

Intervention(s)

Trade Name: Caelyx
Product Name: Caelyx
Product Code: not applicable
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Doxorubicin hydrochloride (liposomal)
CAS Number: 23214-92-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: only oral Cyclophosphamide 50 mg drug products with a marketing authorization will be used
Product Name: Endoxan
Product Code: not applicable
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: only oral Methotrexate 2.5 mg drug products with a marketing authorization are used
Product Name: Methotrexat Wyeth
Product Code: not applicable
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Secondary Objective:

Primary end point(s): Breast cancer free interval (events are reappearance of invasive breast cancer at any site including contralateral breast cancer)

Main Objective: The overall aim of the CASA trial is to investigate the role of PLD as adjuvant chemotherapy for older postmenopausal women (66 years old and above). The stratified analysis combining the results of both randomization options will provide the primary evidence on the effectiveness of PLD. This analysis will assess PLD versus non-PLD-containing control groups (either nil or CM). In addition, analyses will be conducted separately for each of the two randomization options (adjusted for multiple comparisons) to assess each of the individual pair-wise contributions to the overall result.

Secondary ID(s)

2005-003434-18-SE

IBCSG 32-05/ BIG 1-05

Ethics review

Status: Approved
Approval date: 21/09/2007
Contact:

Results

• Results available: Yes
• Date Posted: 17/03/2021
• Date Completed: 31/12/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003434-18/results