Safety and Efficacy Study of Glufosfamide in Previously Treated Advanced Soft Tissue Sarcoma

An Open-Label Phase 2 Study of the Efficacy and Safety of Glufosfamide in Previously Treated Advanced Soft Tissue Sarcoma

Primary Objective:

1. To evaluate the efficacy of glufosfamide in subjects with advanced soft tissue sarcoma as measured by objective response rate

Secondary Objectives:

1. To evaluate the efficacy of glufosfamide in subjects with advanced soft tissue sarcoma as measured by duration of response, progression-free survival and overall survival
2. To evaluate the safety of glufosfamide in subjects with advanced soft tissue sarcoma

Exploratory Objectives:

1. To evaluate the biological effect of glufosfamide on the metabolic profile in subjects with advanced soft tissue sarcomas, as determined by FDG-PET
2. To correlate efficacy endpoints with expression of tumor-associated glucose transporter proteins

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Glufosfamide

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Premiere Oncology of Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Division of Oncology
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Research and Treatment Center
  • New York
    • New York, New York, United States, 10011
      • St. Vincent's Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• Pathologically confirmed diagnosis of soft tissue sarcoma
• Locally advanced unresectable or metastatic disease with no standard curative therapy available that has progressed since the most recent therapy
• Measurable disease by RECIST criteria with at least one target lesion
• 1 or 2 prior chemotherapy/systemic therapy regimens for advanced disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
• A minimum of 3 weeks between prior chemotherapy, radiation therapy, immunotherapy, or other anti-tumor therapy and study entry
• Recovered from reversible toxicities of prior therapy
• Hemoglobin ≥ 9.0 g/dL, neutrophils ≥ 1,500/µL, platelets ≥ 100,000/µL
• Total bilirubin ≤ 1.5-fold ULN, AST/ALT ≤ 2.5-fold ULN (≤ 5-fold if liver metastases)
• Normal creatinine clearance (≥85 mL/min for men and ≥75 mL/min for women; calculated by Cockcroft-Gault formula
• All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) from entry into the study through 6 months after the last dose

Exclusion Criteria:

• Soft tissue sarcoma of the following subtypes: gastrointestinal stromal tumor (GIST), alveolar soft parts sarcoma, hemangiopericytoma and Kaposi's sarcoma
• Most recent relapse occurring during treatment with ifosfamide within 4 weeks of last dose
• Symptomatic brain or leptomeningeal metastases
• Active clinically significant infection requiring antibiotics
• Recent (one year) history or symptoms of cardiovascular disease (NYHA Class 2, 3, or 4), particularly coronary artery disease, arrhythmias or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, cerebrovascular accident or congestive heart failure
• Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
• Major surgery within 3 weeks of the start of study treatment, without complete recovery
• Females who are pregnant or breast-feeding
• Participation in an investigational drug or device study within 21 days of study entry
• Concomitant disease or condition that could interfere with the conduct of the study, or that in the opinion of the investigator would pose an unacceptable risk to the subject in this study
• Unwillingness or inability to comply with the study protocol for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glufosfamide	Drug: Glufosfamide; 5000 mg/m2 of glufosfamide on Day 1 of each three-week cycle for up to 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The event rate was the response rate (complete and partial response) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0). The associated 95% exact binomial confidence intervals were calculated.	Tumor assessments were performed at baseline and every 6 weeks until disease progression was documented.

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival	All subjects were followed regularly until glufosfamide discontinuation, tumor progression or additional antitumor therapy was started and then were followed for survival at 3 month intervals for the first year and once every year thereafter until death.
Overall Survival	All subjects were followed regularly until glufosfamide discontinuation, tumor progression or additional antitumor therapy was started and then were followed for survival at 3 month intervals for the first year and once every year thereafter until death.

Collaborators and Investigators

• Sponsor: Eleison Pharmaceuticals LLC.
• Collaborators: Threshold Pharmaceuticals
• Investigators: Principal Investigator: Lee Cranmer, MD, PhD, University of Arizona; Principal Investigator: Claire Verschraegen, MD, University of New Mexico Cancer Center; Principal Investigator: David Mendelson, MD, Premiere Oncology of Arizona; Principal Investigator: Douglas Adkins, MD, Washington University School of Medicine, Division of Oncology; Principal Investigator: Gina D'Amato, MD, H. Lee Moffitt Cancer Center; Principal Investigator: Gerald Rosen, MD, St. Vincent's Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 27, 2007
• First Submitted That Met QC Criteria: February 27, 2007
• First Posted (Estimate): March 1, 2007

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 3, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: TH-CR-305