Everolimus (RAD001) and Carboplatin in Pretreated Metastatic Breast Cancer

Everolimus (RAD001) in Combination With Intravenous Carboplatin in Taxane- and Anthracycline-pretreated Patients With Progressive Metastatic Breast Cancer

This is an open-label, mono-center phase I/II study designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of RAD001 in combination with carboplatin in taxane- and anthracycline-pretreated patients with progressive metastatic breast cancer. Additionally, the study is designed to characterize the safety, the tolerability and efficacy of this study.

During the phase I part the study will include at least 3 patients at each dose-level until MTD is reached. Each cohort will consist of newly enrolled patients. Intra-patient dose escalation is not permitted. Once MTD is reached a total of 6 patients will be treated at MTD (phase I). For the phase II the minimax two-stage design will be applied. After testing the drug on 16 patients in the first stage of phase II, the trial will be terminated if 1 or fewer respond (SD, PR, CR). If the trial goes on to the second stage, a total of 34 patients will be studied during the phase II part.

Inclusion Criteria:

• adult female patients
• at least two prior chemotherapies due to metastatic or inoperable breast cancer
• Karnofsky performance status of at least 60%
• pretreatment with at least one taxane and one anthracycline

Exclusion Criteria:

• previous treatment with mTOR-inhibitors, carboplatin, cisplatin or oxaliplatin
• inadequate organ function including bone marrow function
• bleeding tumours
• known uncontrolled metastases in CNS or carcinomatous meningosis
• patients who have been treated during the last five days with inhibitors or inducers of CYP3A
• serious pulmonary, neurological, endocrinological or other disorders interfering with this study medication, especially patients with known lung fibrosis, emphysema or severe COPD