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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00949325
• Other study ID #: J0963
• Secondary ID: NA_00028490
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2009
• Est. completion date: September 2012

Study information

• Verified date: March 2019
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

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.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Comprehensive Cancer Network, Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 tissu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Incidence of Dose Limiting Toxicities	Dose limiting toxicities in each dose cohort.	End of second 28-day cycle
Primary	Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2	Number of days from day 1 of treatment until date of death from any cause.	up to 5 years
Secondary	Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2	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.	up to 3 years
Secondary	Objective Response Rate	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	up to 5 years
Secondary	Maximum Observed Plasma Concentration (Cmax)	Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS	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.
Secondary	Area Under the Curve (AUC)	AUC was calculated using a single compartment model.	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.
Secondary	Drug Clearance	Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.	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.
Secondary	Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2	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	up to 3 years
Secondary	Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2		up to 5 years
Secondary	Time to Response	Number of days after 2 cycles of treatment, until maximal response is observed.	up to 5 years
Secondary	Duration of Response	Number of days until documentation of disease progression or date of death from other cause	up to 5 years
Secondary	Clinical Benefit Rate	Number of days from documented improvement to disease progression.	up to 5 years