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

April 10, 2012 updated by: Radboud University Medical Center

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GH
        • Recruiting
        • University Medical Center Nijmegen st Radboud
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: temsirolimus/PLD
temsirolimus (Torisel) with pegylated liposomal doxorubicin (PLD,Doxil,Caelyx);a dose escalating study in a 3+3 design
Drug: Temsirolimus/PLD
This is a dose escalation study. Patients will start with temsirolimus iv once weekly. After 2 weeks, PLD therapy is added. From then on, PLD is repeated every 4 weeks. One cycle is 28 days. The DLT period is also defined within the first 28 days of combination therapy (thus the first 6 weeks of study participation). The first dose level (DL) is DL 1. Depending on toxicity, intermediate dose levels can be added. If no MTD is found in the sixth cohort, this dose level will be considered as the recommended dose (RD), being the optimal dose for both drugs in this combination. At the MTD dose level, the dose level will be expanded to a total of 12 patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MTD, pharmacokinetic parameters
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Effectiveness: objective response rate, time to progression
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

February 1, 2012

Study Completion (Anticipated)

August 1, 2012

Study Registration Dates

First Submitted

September 17, 2009

First Submitted That Met QC Criteria

September 22, 2009

First Posted (Estimate)

September 23, 2009

Study Record Updates

Last Update Posted (Estimate)

April 11, 2012

Last Update Submitted That Met QC Criteria

April 10, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCNONCO200902

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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