Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma
- Registration Number
- NCT00949325
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description temsirolimus plus liposomal doxorubicin temsirolimus plus liposomal doxorubicin Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.
- Primary Outcome Measures
Name Time Method Part 1: Incidence of Dose Limiting Toxicities End of second 28-day cycle Dose limiting toxicities in each dose cohort.
Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 up to 5 years Number of days from day 1 of treatment until date of death from any cause.
- Secondary Outcome Measures
Name Time Method Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 up to 5 years Maximum Observed Plasma Concentration (Cmax) 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
Area Under the Curve (AUC) 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.
Drug Clearance 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.
Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 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
Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2 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.
Clinical Benefit Rate up to 5 years Number of days from documented improvement to disease progression.
Objective Response Rate 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
Time to Response up to 5 years Number of days after 2 cycles of treatment, until maximal response is observed.
Duration of Response up to 5 years Number of days until documentation of disease progression or date of death from other cause
Trial Locations
- Locations (1)
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States