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)
- Conditions
- 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: 8.1Level: LLTClassification code 10006188Term: Breast cancer female NOS
- Registration Number
- EUCTR2005-003434-18-FR
- Lead Sponsor
- International Breast Cancer Study Group (IBCSG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 77
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Objective: ;Primary end point(s): Breast cancer free interval (events are reappearance of invasive breast cancer at any site including contralateral breast cancer)
- Secondary Outcome Measures
Name Time Method