Brief Title
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
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
MTD, pharmacokinetic parameters
Secondary Outcome
Effectiveness: objective response rate, time to progression
Condition
Advanced/Recurrent Breast Cancer
Intervention
Temsirolimus/PLD
Study Arms / Comparison Groups
temsirolimus/PLD
Description: temsirolimus (Torisel) with pegylated liposomal doxorubicin (PLD,Doxil,Caelyx);a dose escalating study in a 3+3 design
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
June 2009
Completion Date
August 2012
Primary Completion Date
February 2012
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
C.M.L. van Herpen, MD, Phd, +31 24 3610353, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT00982631
Organization ID
UMCNONCO200902
Responsible Party
Sponsor
Study Sponsor
Radboud University Medical Center
Study Sponsor
C.M.L. van Herpen, MD, Phd, Principal Investigator, UMCN st Radboud
Verification Date
April 2012