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

NCT00949325 | Completed Phase 1 Results

• 2 other identifiers: J0963NA_00028490
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Part 1: Incidence of Dose Limiting Toxicities

  Dose limiting toxicities in each dose cohort.

  End of second 28-day cycle

• 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 Outcomes (10)

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

  up to 3 years

• Objective Response Rate

  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.

• 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.

• 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.

Study Arms (1)

temsirolimus plus liposomal doxorubicin

EXPERIMENTAL

Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.

Drug: temsirolimus plus liposomal doxorubicin

Interventions

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.

Also known as: Torisel, Doxil

temsirolimus plus liposomal doxorubicin

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Comprehensive Cancer Network: collaborator
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Related Publications (2)

• 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.

  PMID: 23382028 RESULT

• 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.

  PMID: 30410720 DERIVED

MeSH Terms

Conditions

Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Leiomyosarcoma; Sarcoma, Ewing; Chondrosarcoma; Liposarcoma; Histiocytoma, Malignant Fibrous; Neurofibrosarcoma; Sarcoma, Synovial

Interventions

temsirolimus; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Adipose Tissue; Histiocytoma; Neoplasms, Fibrous Tissue; Fibrosarcoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: David M. Loeb, M.D., Ph.D.
• Organization: Johns Hopkins University

loebda@jhmi.edu

410-502-7247

Study Officials

• David M Loeb, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 30, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: March 11, 2019
• Results First Posted: March 11, 2019

Record last verified: 2019-03

Locations

US (1)