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Trial record 50 of 2158 for:    doxorubicin

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

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ClinicalTrials.gov Identifier: NCT00949325
Recruitment Status : Completed
First Posted : July 30, 2009
Results First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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 plus liposomal doxorubicin 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.

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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 study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.
Drug: temsirolimus plus liposomal doxorubicin
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 Outcome Measures :
  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 Outcome Measures :
  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.



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

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

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 ClinicalTrials.gov identifier (NCT number): NCT00949325


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

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00949325     History of Changes
Other Study ID Numbers: J0963
NA_00028490 ( Other Identifier: JHMI-IRB )
First Posted: July 30, 2009    Key Record Dates
Results First Posted: March 11, 2019
Last Update Posted: March 11, 2019
Last Verified: March 2019
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
osteosarcoma
soft tissue sarcoma
rhabdomyosarcoma
leiomyosarcoma
Ewing's sarcoma
chondrosarcoma
liposarcoma
malignant fibrous histiocytoma
malignant peripheral nerve sheath tumor
pleiomorphic sarcoma
spindle cell sarcoma
synovial sarcoma
cancer stem cell
Additional relevant MeSH terms:
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Doxorubicin
Liposomal doxorubicin
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sirolimus
Everolimus
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