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

Phase 1

• Conditions: Advanced/Recurrent Breast Cancer; Endometrial Cancer; Ovarian Cancer
• Interventions: Drug: Temsirolimus/PLD

• Registration Number: NCT00982631
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-09-17
• Study First Submitted QC: 2009-09-22
• Study First Posted: 2009-09-23
• Primary Completion: 2012-02
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-10
• Last Update Posted: 2012-04-11
• Study Completion: 2012-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• 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: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
temsirolimus/PLD	Temsirolimus/PLD	temsirolimus (Torisel) with pegylated liposomal doxorubicin (PLD,Doxil,Caelyx);a dose escalating study in a 3+3 design

Primary Outcome Measures

Name	Time	Method
MTD, pharmacokinetic parameters	2 years

Secondary Outcome Measures

Name	Time	Method
Effectiveness: objective response rate, time to progression	2 years

Trial Locations

Locations (1)

University Medical Center Nijmegen st Radboud; 🇳🇱 Nijmegen, Gelderland, Netherlands