Safety and Efficacy Study of Glufosfamide in Ovarian Cancer

Phase 2

Terminated

Conditions: Ovarian Cancer

Interventions: Drug: Glufosfamide

Registration Number: NCT00442598

Lead Sponsor: Eleison Pharmaceuticals LLC.

Brief Summary: 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

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 17

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (10): California Cancer Center
🇺🇸
Greenbrae, California, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
New Mexico Cancer Care Alliance
🇺🇸
Albuquerque, New Mexico, United States
UCI Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
Premiere Oncology of Arizona
🇺🇸
Scottsdale, Arizona, United States
Louisville Oncology Clinical Research Program
🇺🇸
Louisville, Kentucky, United States
Indiana University Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Gabrail Cancer Center
🇺🇸
Canton, Ohio, United States
Gynecologic Oncology Research & Development, LLC
🇺🇸
Greenville, South Carolina, United States
Harrington Cancer Center
🇺🇸
Amarillo, Texas, United States