Clinical trial NCT00949325: Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma
Official title: Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sarcoma
Keywords: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2009-07-30
Enrollment: 24
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Part 1: Incidence of Dose Limiting Toxicities
timeFrame: End of second 28-day cycle
measure: Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
timeFrame: up to 5 years
Secondary outcomes:
measure: Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
timeFrame: up to 3 years
measure: Objective Response Rate
timeFrame: up to 5 years
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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.
measure: Area Under the Curve (AUC)
timeFrame: 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.
measure: Drug Clearance
timeFrame: 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.
measure: Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
timeFrame: up to 3 years
measure: Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
timeFrame: up to 5 years
measure: Time to Response
timeFrame: up to 5 years
measure: Duration of Response
timeFrame: up to 5 years
measure: Clinical Benefit Rate
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: David M Loeb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thornton KA, Chen AR, Trucco MM, Shah P, Wilky BA, Gul N, Carrera-Haro MA, Ferreira MF, Shafique U, Powell JD, Meyer CF, Loeb DM. A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma. Int J Cancer. 2013 Aug 15;133(4):997-1005. doi: 10.1002/ijc.28083. Epub 2013 Mar 4.
citation: Trucco MM, Meyer CF, Thornton KA, Shah P, Chen AR, Wilky BA, Carrera-Haro MA, Boyer LC, Ferreira MF, Shafique U, Powell JD, Loeb DM. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018 Nov 5;8:21. doi: 10.1186/s13569-018-0107-9. eCollection 2018.