Clinical trial NCT00982631: A Study of Combination of Temsirolimus (Torisel®) and Pegylated Liposomal Doxorubicin (PLD, Doxil®/Caelyx®) in Advanced or Recurrent Breast, Endometrial and Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced/Recurrent Breast Cancer
Endometrial Cancer
Ovarian Cancer
Keywords: temsirolimus (Torisel®)
pegylated liposomal doxorubicin (PLD, Doxil®/ Caelyx®)
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2009-09-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MTD, pharmacokinetic parameters
timeFrame: 2 years
Secondary outcomes:
measure: Effectiveness: objective response rate, time to progression
timeFrame: 2 years
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen st Radboud
state: Gelderland
Study officials:
affiliation: UMCN st Radboud
name: C.M.L. van Herpen, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References: