A Study of Combination of Temsirolimus (Torisel®) and Pegylated Liposomal Doxorubicin (PLD, Doxil®/Caelyx®) in Advanced or Recurrent Breast, Endometrial and Ovarian Cancer

• Status: Unknown status
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

A study to examine the combination of temsirolimus and Caelyx® (chemotherapeutic) in advanced or recurrent breast, endometrial and ovarian cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Treatments: Doxorubicin; Everolimus; Liposomal doxorubicin; Sirolimus

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