Cancer of the prostate prostatic neoplasm.
Conditions
Interventions
Everolimus treatment will be prescribed at two dose levels. The first ten
included patients will be treated at a dose of 5 mg once daily. In case of * 20
% Grade 3 toxicity after 6 weeks of treatmen
Sponsors
Nederlands Kanker Instituut
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Prostate cancer diagnosis and a rising PSA under castrate serum testosterone levels (2 rises in a period of at least 3 months), PSA > 10ng/ml. - At least one prior cycle of Docetaxel treatment. - ECOG performance status 0-2. - Locally accessible prostate cancer for TRUS-guided biopsies. - Written informed consent. - Laboratory requirements: a) Hematology: * Hemoglobin > 5 mmol/L * Platelet count * 100,000/*L * No leucopenia b) Hepatic function: * AST and ALT * 2.5 times upper limit of normal (ULN) * Bilirubin * 1.5 times ULN c) Renal function: * Calculated GFR (Cockroft) * 60 ml/min * PT/PTT normal (no anticoagulants) - Fertile patients must use effective contraception during and for 6 months after completion of study therapy.
Exclusion criteria
Exclusion criteria: - Small cell pathology. - Allergy to Everolimus or cyclophosphamide or components of Afinitor ® or Endoxan ®. - Co-medication interfering with CYP3A4 activity. - Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of Everolimus, including any of the following: o Ulcerative disease o Vomiting o Diarrhea o Malabsorption syndrome - Other active malignancy or malignancy at * 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer . - Recent (within 2 weeks) surgery. - Uncontrolled concurrent illness including, but not limited to, any of the following: o Ongoing or active infection (e.g., bacterial, viral or fungal) o Severely impaired lung function o Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN) o Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis) o Symptomatic congestive heart failure o Unstable angina pectoris o Cardiac arrhythmia - Lower urinary tract obstruction not treated with bladder catheterisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In order to investigate the mTOR inhibition in the prostate by Everolimus and the possible synergistic interaction with low dose, metronomic, oral Cyclophosphamide treatment, phophorylation of 4eBP1 and p70S6K will be assessed in prostate biopsies of prostate cancer patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| PSA response Toxicity of the combined Everolimus and Cyclophosphamide treatment | — |
Countries
Netherlands
Outcome results
None listed