advanced or therapy refractory breast cancer, endometrial cancer, or ovarian cancer.
Conditions
Interventions
Trade Name: Torisel
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Caelyx
Pharmaceutical Form: Intravenous infusion
Sponsors
University Medical Centre Nijmegen St Radboud
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients with proven advanced breast cancer, endometrial cancer or ovarian cancer, who are refractory to standard therapies or for whom no standard therapy exists. •Age = 18 years •Patients who have an ECOG status of 0 or 1 •Patients who have a life expectancy of at least 12 weeks •Negative pregnancy test for female patients of childbearing potential •Signed informed consent 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
Exclusion criteria: •Adequate bone marrow: neutrophils = 1.5 x 109/L, platelets = 100 x 109/L and haemoglobin = 5.0 mmol/l •Adequate renal function: GFR = 60 ml/min •Adequate liver function: ALT and AST grade 2). •Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C •Clinically symptomatic brain or meningeal metastasis. Patients with seizure disorders requiring medication (such as steroids or antiepileptics). Concomitant treatment with strong CYP3A4 inductors (such as rifampicin, St. John´s Wort) or CYP3A4 inhibitors (such as ketoconazole, voriconazole, itraconazole, diltiazem, verapamil, erythromycin) within 2 weeks prior to start. •Moderate or weak CYP3A4 modifiers should be used concomitantly only after careful assessment of risk-benefit ratio. Concomitant use of carbamazepine, phenobarbital, phenytoin or chronic use of dexamethasone is not allowed. (Table 1) •Other concomitant anti-cancer therapy (except steroids) •Concomitant use of streptozocin, mercaptopurine. •Previous treatment with one of the study drugs. •Previous treatment with other mTOR inhibitors •Prior investigational therapy/agents within 4 weeks of start, in case of bevacizumab at least 60 days between bevacizumab discontinuation and first dosing of temsirolimus. •Surgical treatment or radiation therapy in the past 4 weeks. Palliative radiotherapy at focal sites on the extremities is allowed, also within 4 weeks before start •Unresolved toxicity CTC = grade 2 from previous anti-cancer therapy except alopecia. •Known or suspected allergy to any investigational agent or any agent given in association with this trial. •Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results •Any condition that is unstable or which could jeopardize the safety of patient and his compliance in the study. •Antracyclines: > 450 mg/m2 doxorubicin or and > 600 mg/m2 epirubicin •Medications known to have dysrhythmic potential is not permitted (ie, terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide) •Usage of coumarin-derivate anticoagulants. Low molecular weight heparin is permitted and advised.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Maxiumum tolerated dose for the combination of temsirolimus and PLD.;Main Objective: The primary objective of this Phase 1b study is to identify the maximum tolerated dose (MTD) and recommended phase II dose of the combination of temsirolimus and Caelyx® in patients with advanced or therapy refractory breast cancer, endometrial cancer, or ovarian cancer.;Secondary Objective: To assess the safety and toxicity profile. To assess the pharmacokinetic profile of the combination of temsirolimus and PLD. To assess the anti tumour activity of the combination of temsirolimus and PLD. To assess the early effect on tumor metabolism by FDG-PET (baseline, after 2 and 6 weeks) To assess the effects on regulatory T cells, the IGF pathway and on circulating tumour cells (CTCs) and circulating endothelial cells (CECs). | — |
Countries
Netherlands
Outcome results
None listed