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

Recruiting

• Conditions: 10035227; advanced or recurrent breastcancer; breast cancer; endometrial cancer; ovarian cancer

• Registration Number: NL-OMON33331
• Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 30

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>MTD, pharamcokinetic parameters</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Effectiveness: objective response rate, time to progression<br /><br>FDG-PET: kwalitative and kwantitative (SUV)<br /><br>CTC and CEC: numbers</p><br>