Clinical trial NCT00442598: Safety and Efficacy Study of Glufosfamide in Ovarian Cancer
Official title: An Open-Label Phase 2 Study of the Safety and Efficacy of Glufosfamide in Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian
Cancer
CA-125
Third-line
Glufosfamide
Lead sponsor: Eleison Pharmaceuticals LLC.
Sponsor class: INDUSTRY
First posted: 2007-03-02
Enrollment: 17
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: CA 125 Response Rate
timeFrame: Duration of study, up to 18 weeks.
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Duration of study, up to 18 weeks.
measure: Progression-free Survival
timeFrame: Median measured in months
measure: Overall Survival
timeFrame: Median measured in months, until death or censorship at analysis.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Premiere Oncology of Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Greenbrae
country: United States
facility: California Cancer Center
state: California
city: Orange
country: United States
facility: UCI Chao Family Comprehensive Cancer Center
state: California
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Louisville Oncology Clinical Research Program
state: Kentucky
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Greenville
country: United States
facility: Gynecologic Oncology Research & Development, LLC
state: South Carolina
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
Study officials:
affiliation: University of Arizona
name: David Alberts, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Premiere Oncology of Arizona
name: Michael Gordon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: Daniela Matei, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: California Cancer Center
name: Peter D Eisenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gynecologic Oncology Research & Development, LLC
name: Larry Puls, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCI Chao Family Comprehensive Cancer Center
name: Krishnansu Tewari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gabrail Cancer Center
name: Nashat Gabrail, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Louisville Oncology Clinical Research Program
name: Jeffrey Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New Mexico Cancer Research Alliance
name: Claire Verschraegen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Harrington Cancer Center
name: William Robinson, MD
role: PRINCIPAL_INVESTIGATOR
References: