Breast cancer is the most prevalent malignancy in women and metastatic breast cancer is a leading cause of mortality, accounting for more than 400,000 deaths annually worldwide. Even though anthracyclines and taxanes are the most active agents in breast cancer, treatment failure occurs in a substantial number of patients and median survival for breast cancer remains 2 to 3 years. Hence, the combination of chemotherapy with less hematotoxic agents is a promising approach.
Conditions
Interventions
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Current Sponsor code: Carboplatin
Product Name: Everolimus
Sponsors
Charité - University Hospital of Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adult, female patients (= 18 years old) • Histologically or cytologically proven breast cancer that is now progressive (metastatic or locally recurrent) and inoperable. • At least two prior chemotherapy regimens due to metastatic or inoperable breast cancer. • Pretreatment with at least one taxane and one anthracycline (separated or combined) in an adjuvant or metastatic setting. • Completion of all prior chemotherapy, immunotherapy, targeted non-cytotoxic therapy and radiotherapy two weeks prior to first dose on study. Concomitant treatment with bisphosphonates is possible. • Karnofsky performance status of al least 60% • Signed written informed consent according to ICH/EU GCP and national/local regulations • Infertility or acceptable method of contraception (PEARL - Index =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Known hypersensitivity against everolismus or sirolimus (rapamycin), carboplatin, or lactose. • Previous treatment with cisplatin, carboplatin, or oxaliplatin. • Previous treatment with RAD001 (Everolimus) or other mTOR-inhibitors • HER2-positive patients who are candidates for trastuzumab • Known uncontrolled metastases in CNS or Meningeosis carcinomatosa. • Prevalence of a hypercholesterinemia/hypertriglyceridemia (> CTC grade 3). • Uncontrolled infection. • Serious cardiac disease (uncontrolled arrhythmias, unstable angina, severe congestive heart failure). • Serious pulmonary, neurological, endocrinological or other disorder interfering with study medication, especially patients with known lung fibrosis, emphysema, or severe COPD. • Bleeding tumor • Serious depression that needed therapy within the last 5 years. • Missing willingness or ability to comply with scheduled visits, treatment plans, laboratory tests, or other study procedures • Concomitant or previous malignancies other than basal cell or squamous cell skin cancer, in situ cervical cancer and other cancer for which the patient has been disease-free for at least 5 years. • Unresolved hepatitis B or C infection or known HIV positive infection. • Inadequate organ function including bone marrow function (WBC = 2.5 x 109/L, ANC = 1.5 x 109/L, Platelets = 80 x 109/L, or Hb = 8 g/dL), liver function (total bilirubin > 1.0 x ULN > 1.5 x ULN, albumin = 3g/dl, serum transaminase activity = 2.5 x ULN or = 5.0 x ULN if the elevation is due to hepatic metastasis, alkaline Phosphatase = 2.5 x ULN or 5.0 if the elevation is due to hepatic metastasis), renal function (creatinine = 2 x ULN) • Patients who received any other investigation drugs within 30 days prior study enrolment • Patients who have been treated during the last five days with inhibitors or inducers the isoenzyms CYP3A (e.g. rifabutin, rifampicin, clarithromycin, ketoconazol, itroconazol, voriconazol, ritinavir, telithromycin). • Women who are pregnant or breast feeding, or women of childbearing potential without highly effective contraception (PEARL-Index < 1%) (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to study enrolment). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. • Persons who are detained officially or legally to an official institute according AMG § 40
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of phase I: To evaluate the safety and optimal dose of RAD001 in combination with carboplatin in taxane- and anthracycline-pretreated patients with progressive metastatic breast cancer. Primary objective of phase II: Response Rate (SD, PR and CR) ;Secondary Objective: Secondary objectives of Phase II: Duration of response, duration of progression-free survival, clinical benefit, safety and tolerability ;Primary end point(s): Phase I: number of patients with DLT at each RAD001 dose level investigated Phase II: response rate (CR / PR / SD) according to RECIST | — |
Countries
Germany
Outcome results
None listed