MedPath

Everolimus (RAD001) in combination with intravenous carboplatin in taxane- and anthracycline-pretreated patients with progressive metastatic breast cancer - RAD001 and carboplatin in pretreated metastatic breast cancer

Phase 1
Conditions
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.
Registration Number
EUCTR2008-006055-52-DE
Lead Sponsor
Charité - University Hospital of Berlin
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Female
Target Recruitment
58
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 < 1%)
o Completion of one or more of the following criteria:
- female of non-childbearing potential: hysterectomy, bilateral oophorectomy, bilateral tube ligation, post-menopausal = 2 years
- female with acceptable contraception: complete abstinence of intercourse, intrauterine device, two forms of barriers contraception, male partner is sterile and the only partner of the female
• Subject is able to understand and comply with the protocol requirements and instructions and intends to complete the study as planned
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
© Copyright 2025. All Rights Reserved by MedPath