Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00949325
Recruitment Status : Completed
First Posted : July 30, 2009
Last Update Posted : November 26, 2014
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

Brief Summary:
The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma. A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.

Condition or disease Intervention/treatment Phase
Sarcoma Drug: temsirolimus (Torisel) plus liposomal doxorubicin (Doxil) Phase 1 Phase 2

Detailed Description:
The effectiveness of treatments for recurrent sarcomas is quite limited. One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas
Study Start Date : September 2009
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Arm Intervention/treatment
Experimental: Temsirolimus plus Liposomal Doxorubicin
Single arm: Temsirolimus is administered IV in cohorts of sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at a dose of 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Treatment with Temsirolimus may continue beyond 2 years.
Drug: temsirolimus (Torisel) plus liposomal doxorubicin (Doxil)
Patients will be treated with temsirolimus weekly by iv and with liposomal doxorubicin (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.
Other Names:
  • Torisel
  • Doxil

Primary Outcome Measures :
  1. Incidence of dose limiting toxicities [ Time Frame: 2 months ]

Secondary Outcome Measures :
  1. To describe the pharmacokinetics of Torisel when administered with liposomal doxorubicin [ Time Frame: 2 weeks ]
  2. Progression-free survival [ Time Frame: 2-4 months ]
  3. Time to response [ Time Frame: 2-4 months ]
  4. Clinical benefit rate [ Time Frame: 2-4 months ]
  5. Overall survival [ Time Frame: 1 year ]
  6. To assess the activity of the mTOR signaling pathway before and after therapy with Torisel and liposomal doxorubicin [ Time Frame: 2 months ]
  7. To measure the proportion of cells with stem cell properties in tumors before and after treatment with Torisel and liposomal doxorubicin [ Time Frame: 2 months ]
  8. objective response rate [ Time Frame: 2-4 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed sarcoma that is recurrent or refractory to conventional treatment
  • Measurable disease by RECIST criteria
  • ECOG performance status < 2 (or Lansky/Karnofsky > 60% for children)
  • Life expectancy greater than 3 months
  • Adequate organ function
  • absolute neutrophil count at least 1,500
  • platelets at least 100,000
  • bilirubin less than 1.5 x upper limit of normal
  • AST and ALT less than 2.5 x upper limit of normal
  • creatinine less than 1.5 x upper limit of normal OR creatinine clearance at least 60 ml/min/1.73 m2
  • fasting serum cholesterol less than 350
  • fasting serum triglycerides less than 400
  • PT or INR less than 1.3 x upper limit of normal
  • normal urinalysis
  • Ability to understand and sign the informed consent document

Exclusion Criteria:

  • Prior chemotherapy or radiotherapy within 3 weeks of entering the study (6 weeks for nitrosoureas or mitomycin C)
  • Prior treatment with a tyrosine kinase inhibitor within 10 days of entering the study
  • History of pulmonary hypertension or pneumonitis
  • Patients may not be receiving other investigational agents
  • Prior therapy with rapamycin, rapamycin analogues, or tacrolimus
  • Uncontrolled brain metastases
  • History of grade 3 or 4 hypersensitivity to macrolide antibiotics
  • Concurrent treatment with immunosuppressive agents other than a stable (for more than 2 weeks) dose of corticosteroids
  • Uncontrolled intercurrent illness
  • Pregnancy or breast feeding
  • HIV-positive patients on combination antiretroviral therapy
  • Grade 3 or 4 proteinuria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00949325

United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: David M Loeb, MD, PhD Sidney Kimmel Comprehensive Cancer Center

Publications of Results:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00949325     History of Changes
Other Study ID Numbers: J0963
NA_00028490 ( Other Identifier: JHMI-IRB )
First Posted: July 30, 2009    Key Record Dates
Last Update Posted: November 26, 2014
Last Verified: June 2014

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
malignant peripheral nerve sheath tumor
soft tissue sarcoma
Ewing's sarcoma
malignant fibrous histiocytoma
pleiomorphic sarcoma
spindle cell sarcoma
synovial sarcoma
cancer stem cell

Additional relevant MeSH terms:
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents