E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
3.1 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.
3.2 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.
3.3 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).
3.5 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.
3.6 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.
3.7 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
3.8 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 impairment that interferes with QL assessment or inability to read any of the languages available on the forms. For non-IBCSG Centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group (see Appendix VII for Group-specific guidelines). - Pathology material should be available for submission for central review as part of the quality control measures for this protocol. - Patients must be accessible for follow-up. - Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines. - Patients should have no psychiatric, addictive, or cognitive disorder that would prevent compliance with protocol requirements. |
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E.4 | Principal exclusion criteria |
3.2 Disease Characteristics: - Patients with locally advanced inoperable breast cancer including inflammatory breast cancer, supraclavicular node involvement, or enlarged internal mammary nodes (unless pathologically negative).
3.4 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Breast cancer free interval (events are reappearance of invasive breast cancer at any site including contralateral breast cancer) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Nil (no adjuvant therapy) |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The first interim efficacy analysis will be performed as soon as possible after 64 events have been reported, approximately two years after trial initiation. The final analysis will be performed after 258 events have been reported. The final results are expected to be available by Q3 2010. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |