Safety and Efficacy Study of Glufosfamide in Ovarian Cancer

An Open-Label Phase 2 Study of the Safety and Efficacy of Glufosfamide in Ovarian Cancer

Primary Objectives:

• To evaluate the effect of glufosfamide on the serum concentrations of CA125 in subjects with ovarian cancer
• To evaluate the safety of weekly glufosfamide dosing in subjects with ovarian cancer as compared with every 21-day dosing

Secondary objectives:

• To evaluate the efficacy of glufosfamide in subjects with ovarian cancer as measured by objective response rate, duration of response, progression-free survival, and overall survival
• To evaluate the pharmacokinetics of glufosfamide and isophosphoramide mustard during and after treatment

Exploratory objective:

• To correlate efficacy endpoints with expression of tumor-associated glucose transporter proteins

Study Overview

• Status: Terminated
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Glufosfamide

Detailed Description

Open-label, multicenter, Phase 2 dose escalation study. Subjects will be randomized to receive either once every three weeks dosing regimen or the weekly dosing regimen. Randomization will utilize a 2:1 ratio with two-thirds of the subjects randomized to the weekly dosing regimen.

In the weekly dosing schedule, treatment with glufosfamide 2,500 mg/m2 will be initiated only after the 1,660 mg/m2 treatment cohort has been enrolled and there is evidence that the dose of 1,660 mg/m2 has been well tolerated (See below Section on Pharmacokinetic/Statistical Analyses).

• Study Type: Interventional
• Enrollment (Actual): 17
• 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
    • Greenbrae, California, United States, 94904
      • California Cancer Center
    • Orange, California, United States, 92868
      • UCI Chao Family Comprehensive Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Louisville Oncology Clinical Research Program
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Cancer Care Alliance
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Gynecologic Oncology Research & Development, LLC
  • Texas
    • Amarillo, Texas, United States, 79106
      • Harrington 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: Female

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 epithelial ovarian cancer, peritoneal serous cancer, or carcinoma of the fallopian tube
• Prior treatment with at least one platinum-based chemotherapy
• Evidence of resistance to most recent platinum-containing regimen (relapsed during or within 6 months after completing chemotherapy)

• Evidence of CA 125 progression after most recent chemotherapy defined as either:

  • CA 125 at least 40 U/mL for patients with elevated CA 125 that decreased to <20 U/mL on therapy; or
  • CA 125 at least 40 U/mL and at least a 50% increase over the nadir value for patients with elevated CA 125 that did not decrease to <20 U/mL on therapy.

CA 125 must meet criteria on two occasions not less than one week apart if the CA 125 has increased by at least 100% (i.e., doubled). There must be 3 consecutive increasing measurements over a period of at least two weeks if the CA 125 has increased by at least 50% but less than 100%.

• Elevated serum CA125 (≥40 U/mL) within 2 weeks prior to starting treatment
• At least one target or nontarget lesion by RECIST
• A minimum of 21 days between prior chemotherapy, radiation therapy, immunotherapy, or other anti-tumor therapy and study entry
• Recovered from reversible toxicities of prior therapy
• ECOG score of 0 or 1
• ANC ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥9 g/dL
• Total bilirubin ≤ 1.5-fold ULN, AST/ALT ≤ 2.5-fold ULN (≤ 5-fold ULN if liver metastases)
• Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault formula)
• All women of childbearing potential must have a negative serum pregnancy test and 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:

• Concomitant or planned hormonal therapy, radiation therapy, biologic therapy, chemotherapy or other systemic antitumor therapy for ovarian cancer other than protocol therapy
• Symptomatic brain metastases
• Active clinically significant infection requiring antibiotics
• Known HIV positive or active hepatitis B or C
• 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, congestive heart failure or stroke
• Other active malignancies (other than treated non-melanoma skin cancer or treated in situ cancer) within the past 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 28 days of the first day of dosing on this study
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glufosfamide q21 days; 1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle	Drug: Glufosfamide
Experimental: Glufosfamide q7 days low; 1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle	Drug: Glufosfamide
Experimental: Glufosfamide q7 days high; 1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle	Drug: Glufosfamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CA 125 Response Rate	Reduction in blood levels of CA 125 of >50% from baseline, confirmed at the next study cycle.	Duration of study, up to 18 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate measured by RECIST v1.0	Duration of study, up to 18 weeks.
Progression-free Survival	Time from initiation of study drug to disease progression or death on study	Median measured in months
Overall Survival	Time from initiation of study drug to death.	Median measured in months, until death or censorship at analysis.

Collaborators and Investigators

• Sponsor: Eleison Pharmaceuticals LLC.
• Investigators: Principal Investigator: Peter D Eisenberg, MD, California Cancer Center; Principal Investigator: David Alberts, MD, University of Arizona; Principal Investigator: Michael Gordon, MD, Premiere Oncology of Arizona; Principal Investigator: Daniela Matei, MD, Indiana University school of Medicine; Principal Investigator: Larry Puls, MD, Gynecologic Oncology Research & Development, LLC; Principal Investigator: Krishnansu Tewari, MD, UCI Chao Family Comprehensive Cancer Center; Principal Investigator: Nashat Gabrail, MD, Gabrail Cancer Center; Principal Investigator: Jeffrey Goldberg, MD, Louisville Oncology Clinical Research Program; Principal Investigator: Claire Verschraegen, M.D., New Mexico Cancer Care Alliance; Principal Investigator: William Robinson, MD, Harrington Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 28, 2007
• First Submitted That Met QC Criteria: March 1, 2007
• First Posted (Estimate): March 2, 2007

Study Record Updates

• Last Update Posted (Estimate): March 10, 2015
• Last Update Submitted That Met QC Criteria: March 6, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Cancer; Ovarian; Glufosfamide; Third-line; CA-125
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: TH-CR-303