Breast Neoplasm
Conditions
Brief summary
The purpose of this study is to evaluate, in a first stage, the safety (incidence of cardiac toxicity) of Caelyx in combination with Trastuzumab and Docetaxel; and in a second stage, the tumor response rate of this regimen. This study will be conducted in approximately 30 centers. A total of approximately 70 to 95 subjects will be enrolled.
Interventions
DRUGPegylated Liposomal Doxorubicin
Stage 1: 25 subjects will be treated with Caelyx IV 30 mg/m\^2 on day 1, every 3 weeks Stage 2: 45 new patients will be treated at the recommended dose level (defined in the first step) on day 1, every 3 weeks.
DRUGDocetaxel
Stage 1 and Stage 2: Docetaxel 60 mg/m2 IV as 1-hour infusion, on day 1, every 3 weeks.
DRUGTrastuzumab
Stage 1 and Stage 2: 4 mg/kg IV 90-minute infusion loading dose. Then 2 mg/kg IV weekly during 6 cycles (18 weeks).
Sponsors
MDS Pharma Services
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Patients must fulfill all the following criteria: * Females aged 18 to 70 years-old. * Willingness to participate in the study and comply with its procedures. * Documented diagnosis of metastatic breast carcinoma (stage IV) Human Epidermal Growth Factor Receptor 2 (HER2) overexpressing (Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization(FISH) +). * No prior chemotherapy for metastatic breast cancer. * Adjuvant or neo-adjuvant chemotherapy is allowed according to the following rules: * patients treated with anthracyclines if all the following conditions are met: * Doxorubicin total dose \<= 300 mg/m\^2 * Epirubicin total dose \<= 480 mg/m\^2 * Chemotherapy-free interval of \> 12 months * no taxane-based adjuvant or neo-adjuvant chemotherapy is allowed; * patients treated with non-anthracycline/taxane adjuvant or neo-adjuvant chemotherapy regimens are freely eligible (i.e. cyclophosphamide/methotrexate/fluorouracil (CMF) or similar regimens). * At least one measurable lesion according to RECIST criteria. * Complete hematologic and biologic baseline evaluation within 2 weeks prior to start of treatment. * Complete Tumor baseline evaluation including a total body computed tomography (CT) scan within 4 weeks prior to start of treatment. * Left ventricular ejection fraction (LVEF) \>= 50% as determined by echocardiogram or Multi Gated Acquisition (MUGA) scan. * World Health Organization (WHO) performance status 0,1. * Life expectancy \> 3 months. * Laboratory requirements : * Hematology : * Neutrophils \> 1.5 x 10\^9/L * Platelets \> 100 x 10\^9/L * Hemoglobin \> 10 g/dL * Hepatic function: * Total bilirubin \<= 1.25 x the upper-normal limits (UNL); * ASAT (Aspartate Aminotransferase or SGOT), ALAT (Alanine aminotransferase or SGPT) \<= 2.5 x the upper-normal limits; * For patients with liver metastases: * Total bilirubin \< 1.5 x the UNL (Upper limit of normal) ; * ASAT and/or ALAT \< 3 x the UNL; * Renal function : * Serum Creatinine \< 1.5 x the UNL. * Women of child bearing potential must have a negative serum pregnancy test and be using adequate contraception. * Patients must be accessible for treatment and follow-up.
Exclusion criteria
Patients will not be enrolled if any of the following criteria apply: * Prior chemotherapy for metastatic disease. * History of prior malignancy in the last 10 years (other than non melanoma skin cancer or excised cervical carcinoma in situ). * Radiation to disease areas within 3 weeks of study initiation. * Symptomatic peripheral neuropathy \> grade 2 according to the National Cancer Institute (NCI) Common Toxicity Criteria. * Other serious illness or medical condition. * LVEF \< 50% as determined by echocardiogram or MUGA scan. * Congestive hearth failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia. * History of significant neurologic or psychiatric disorders including dementia or seizures. * Active infection. * Active peptic ulcer, unstable diabetes mellitus or other contraindications for the use of dexamethasone. * Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening. * Concurrent treatment with corticosteroids used for reasons other than for premedication. However patients receiving chronic treatment with corticosteroids (\> 6 months) at low dose (\< 20 mg of methylprednisolone or equivalent dose of other corticosteroids) for whichever reason are eligible. * Taxane-based adjuvant or neo-adjuvant chemotherapy \< 12 months. * Other concurrent chemotherapy, immunotherapy, radiotherapy or any other investigational medication, for the treatment of the tumor. * Pregnant or breast-feeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria | Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment. | Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Caelyx, Docetaxel, Trastuzumab Stage 1: subjects will receive Caelyx one day every 3 weeks in combination with docetaxel one day every 3 weeks and trastuzumab once weekly during 6 cycles. At the end of this stage, based on the number of cardiac events, subjects will proceed to a second stage or restart with a lower dose of Caelyx.
Stage 2: subjects will be treated with the recommended dose of Caelyx (defined in the first stage) in combination with docetaxel and trastuzumab. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Missing | 1 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Caelyx, Docetaxel, Trastuzumab |
|---|---|
| Age, Customized | 27 years |
| Region of Enrollment Italy | 27 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 27 |
| serious Total, serious adverse events | 6 / 27 |
Outcome results
Primary
Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria
Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response.
Time frame: Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment.
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Caelyx, Docetaxel, Trastuzumab | Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria | Participants who had a complete tumor response | 2 Participants |
| Caelyx, Docetaxel, Trastuzumab | Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria | Participants who had a partial tumor response | 13 Participants |
| Caelyx, Docetaxel, Trastuzumab | Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria | Participants who did not have a tumor response | 11 Participants |