a study of combination of temsirolimus (torisel®) and pegylated liposomal doxorubicin (pld, doxil®/caelyx®) in advanced or recurrent breast, endometrial and ovarian cancer

Conditions: Advanced/Recurrent Breast Cancer; Endometrial Cancer; Ovarian Cancer

Summary: a study to examine the combination of temsirolimus and caelyx® (chemotherapeutic) in advanced or recurrent breast, endometrial and ovarian cancer.

to assess 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.

Eligibility 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 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 \< 2.5 x uln, total bilirubin ≤ 1x uln * fasting level of total cholesterol of no more than 350 mg/dl (9.1 mmol/l) and triglyceride level of no more than 400 mg/l (4.5 mmol/l) * left ventricular ejection fraction (lvef) \< 50% * history of serious cardiac disease * active clinically serious bacterial, viral or fungal infections (\> 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

Keywords: temsirolimus (torisel®) pegylated liposomal doxorubicin (pld, doxil®/ caelyx®)