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

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

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

Study Sponsor

C.M.L. van Herpen, MD, Phd, Principal Investigator, UMCN st Radboud

Verification Date

April 2012