Ovarian Cancer
Conditions
Keywords
Ovarian, Cancer, CA-125, Third-line, Glufosfamide
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).
Interventions
DRUGGlufosfamide
Sponsors
Eleison Pharmaceuticals LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glufosfamide q21 Days 1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle
Glufosfamide | 7 |
| 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
Glufosfamide | 10 |
| 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
Glufosfamide | 0 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | CA125 progression | 0 | 1 | 0 |
| Overall Study | Clinical deterioration | 1 | 2 | 0 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Reduced creatinine clearance | 1 | 0 | 0 |
| Overall Study | Tumor progression | 3 | 4 | 0 |
Baseline characteristics
| Characteristic | Glufosfamide q7 Days Low | Glufosfamide q21 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Categorical >=65 years | 4 participants | 1 participants | 5 participants |
| Age, Categorical Between 18 and 65 years | 6 participants | 6 participants | 12 participants |
| Age, Continuous | 52 years | 60 years | 58 years |
| Gender Female | 10 participants | 7 participants | 17 participants |
| Gender Male | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) Asian | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) Black or African American | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) More than one race | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) White | 10 participants | 7 participants | 17 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 9 / 10 |
| serious Total, serious adverse events | 2 / 7 | 3 / 10 |
Outcome results
Primary
CA 125 Response Rate
Reduction in blood levels of CA 125 of \>50% from baseline, confirmed at the next study cycle.
Time frame: Duration of study, up to 18 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glufosfamide q21 Days | CA 125 Response Rate | Partial response | 1 participants |
| Glufosfamide q21 Days | CA 125 Response Rate | Stable disease | 6 participants |
| Glufosfamide q7 Days Low | CA 125 Response Rate | Partial response | 0 participants |
| Glufosfamide q7 Days Low | CA 125 Response Rate | Stable disease | 10 participants |
Secondary
Objective Response Rate
Objective response rate measured by RECIST v1.0
Time frame: Duration of study, up to 18 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glufosfamide q21 Days | Objective Response Rate | Stable disease | 3 participants |
| Glufosfamide q21 Days | Objective Response Rate | Progressive disease | 4 participants |
| Glufosfamide q7 Days Low | Objective Response Rate | Stable disease | 3 participants |
| Glufosfamide q7 Days Low | Objective Response Rate | Progressive disease | 7 participants |
Secondary
Overall Survival
Time from initiation of study drug to death.
Time frame: Median measured in months, until death or censorship at analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glufosfamide q21 Days | Overall Survival | 5.6 months |
| Glufosfamide q7 Days Low | Overall Survival | 6.8 months |
Secondary
Progression-free Survival
Time from initiation of study drug to disease progression or death on study
Time frame: Median measured in months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glufosfamide q21 Days | Progression-free Survival | 1.2 months |
| Glufosfamide q7 Days Low | Progression-free Survival | 1.9 months |