A Phase Ib Study of Combination of Temsirolimus (Torisel®) and Pegylated Liposomal Doxorubicin (PLD, Doxil®/ Caelyx®) in Advanced or Recurrent Breast, Endometrial and Ovarian Cancer
- 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
- 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
- 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
- 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,
- Usage of coumarin-derivate anticoagulants. Low molecular weight heparin is permitted