Everolimus (RAD001) and Carboplatin in Pretreated Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: RAD001 (Everolimus) in combination with carboplatin
* Drug: RAD001 (Everolimus) in combination with carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: RAD001 (Everolimus) in combination with carboplatin|phase I: dose levels: 2,5 mg, 5 mg, 7,5 mg and 10mg daily in combination with carboplatin AUC2 weekly until progress|
|Drug: RAD001 (Everolimus) in combination with carboplatin|phase 2: 10mg RAD001 in combination with carboplatin|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: dose limiting toxicity |  | after three weeks | 
| Phase II: response rate |  | every six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: adverse events |  | after three weeks |