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Completed

NCT Number: NCT00949325

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

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.

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Key information

Conditions

Sarcoma Chondrosarcoma Fibrosarcoma Histiocytoma Histiocytoma, Malignant Fibrous Leiomyosarcoma Liposarcoma Myosarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Adipose Tissue Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Muscle Tissue Neoplasms, Nerve Tissue Nerve Sheath Neoplasms Nervous System Diseases Nervous System Neoplasms Neurofibroma Neurofibrosarcoma Neuromuscular Diseases Osteosarcoma Peripheral Nervous System Diseases Peripheral Nervous System Neoplasms Rhabdomyosarcoma Sarcoma, Ewing Sarcoma, Synovial

Age range

1 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed sarcoma that is recurrent or refractory to conventional treatment
  • Measurable disease by RECIST criteria
  • ECOG (Eastern Cooperative Oncology Group) 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 (aspartate aminotransferase) and ALT(alanine aminotransferase) 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 (prothrombin) or INR (international normalized ratio) 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

Treatment and study plan

temsirolimus plus liposomal doxorubicin

Drug

Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified. The MTD dose was the standard dose of temsirolimus used for the remainder of the study. Dose modifications were based on protocol parameters for toxicities.

Other names: Torisel, Doxil

Primary outcomes

  1. Part 1: Incidence of Dose Limiting Toxicities

    Time frame: End of second 28-day cycle

    Dose limiting toxicities in each dose cohort.

  2. Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

    Time frame: up to 5 years

    Number of days from day 1 of treatment until date of death from any cause.

Secondary outcomes

  1. Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

    Time frame: up to 3 years

    Interval from Date of start of treatment to date of disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.

  2. Objective Response Rate

    Time frame: up to 5 years

    Number of participants who completed at least 2 treatment cycles with evidence of response. Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

  3. Maximum Observed Plasma Concentration (Cmax)

    Time frame: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.

    Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS

  4. Area Under the Curve (AUC)

    Time frame: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.

    AUC was calculated using a single compartment model.

  5. Drug Clearance

    Time frame: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.

    Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.

  6. Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

    Time frame: up to 3 years

    Interval from start of treatment to disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression

  7. Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

    Time frame: up to 5 years

  8. Time to Response

    Time frame: up to 5 years

    Number of days after 2 cycles of treatment, until maximal response is observed.

  9. Duration of Response

    Time frame: up to 5 years

    Number of days until documentation of disease progression or date of death from other cause

  10. Clinical Benefit Rate

    Time frame: up to 5 years

    Number of days from documented improvement to disease progression.

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other

Collaborators

  • National Comprehensive Cancer Network
  • Wyeth is now a wholly owned subsidiary of Pfizer

Registry information

Official study title

Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Jul 30, 2009
Registry last updated
Mar 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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