Epithelial Ovarian Cancer
Conditions
Keywords
second line treatment, platinum resistant, ovary, ovaries, cancer, epithelial, carcinomas, tumor
Brief summary
The purpose of this study is to evaluate the objective response rate, safety and identify potential biomarkers in platinum-resistant ovarian cancer patients treated with voreloxin injection given on a 28-day cycle.
Detailed description
Other objectives of this study are to evaluate Progression-free survival and measure CA-125 response rate.
Interventions
DRUGVoreloxin Injection
All patients in initial dose level receive voreloxin injection at 48 mg/m2 administered once every 21 days up to 6 cycles. Subsequent levels are of 60 mg/m2 or 75 mg/m2 every 28 days up to 6 cycles if safety acceptable.
Sponsors
Sunesis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer * Completed at least one Platinum Based Therapy (PBT) regimen (carboplatin, cisplatin, or another organoplatinum compound). * Evidence of platinum-resistant disease, relapse/progression within 6 months of the completion of PBT, or intolerant to PBT (inability to receive PBT due to hypersensitivity reactions to platinum) * Patients with primary platinum-resistant disease are allowed to receive no more than one nonplatinum cytotoxic regimen and no more than one noncytotoxic regimen for the management of recurrent or persistent disease after the development of primary platinum-resistance. * Measurable disease per GOG-RECIST criteria * GOG Performance Status of 0 or 1
Exclusion criteria
* Radiotherapy, chemotherapy, and hormonal, cytokine, or targeted therapy, within 3 weeks (nitrosurea or mitomycin C within 6 weeks) prior to the anticipated first day of treatment. * Monoclonal antibody therapy within 4 weeks prior to clinical study entry * Unresolved or impending bowel obstruction * Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia * Prior radiotherapy to more than 25% of the marrow space * Requiring hemodialysis or peritoneal dialysis * Myocardial infarction or cerebrovascular accident/transient ischemic attack within the 6 months prior to the anticipated first day of treatment * Thromboembolic event (deep vein thrombosis \[DVT\] or pulmonary embolus \[PE\]) within 28 days prior to the anticipated first day of treatment * History of active CNS metastases * Any other medical, psychological, or social condition that would contraindicate the patient's participation in the clinical study due to safety or compliance with clinical study procedures. Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria | GOG-RECIST assessment obtained on cycle2, 4 and 6 Day 21for patients treated with 48 mg/m2 SNS-595 and Day 28 for patients treated with 60 mg/m2, through 28 (±14) days afte the last treatment at the end of safety follow up period | Response rate was calculated per investigator's tumor assessment based on GOG-RECIST, which includes radiographic imaging, physical examination results, and CA-125 levels. No independent review of CT scans (lesion assessments) was performed. CR: disappearance of all target and nontarget lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at baseline, is required for ovarian carcinoma studies. PR is \>= 30% decrease in the sum of LD of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Using Kaplan-Meier Methods | From the first teratment of Vosaroxin to the end of Cycle 6 or 28 days after the last treatment at the end of safety follow up period if continued in the extended treatment period | PFS is the the time between the date the patient first received Vosaroxin and the earliest date of disease progression. For patients who experienced disease progression, the date of disease progression will be the earliest date on which disease progression is indicated based on the rules. For patients who died with no indication of disease progression, the date of death will be the earliest date on which death is documented based on the rules. For patients who have no indication of disease progression or death, the censoring date will be the Date of Confirmed Contact from the last Survival Follow-Up CRF, or if not in survival follow-up, then the Assessment Date from the last GOG-RECIST CRF, or if no response assessment available, Date of Last Visit / Contact from Extended Treatment Completion CRF if in extended treatment, or from Cycle 6 Completion / Early Termination CRF if not in extended treatment. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 48 mg/m2 48 mg/m2 every 21 days | 65 |
| 60 mg/m2 60 mg/m2 every 28 days | 37 |
| 75 mg/m2 75 mg/m2 every 28 days | 35 |
| Total | 137 |
Baseline characteristics
| Characteristic | 60 mg/m2 | 75 mg/m2 | 48 mg/m2 | Total |
|---|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 10.51 | 57.6 years STANDARD_DEVIATION 12.13 | 60 years STANDARD_DEVIATION 9.87 | 60.1 years STANDARD_DEVIATION 10.74 |
| BSA (m2) | 1.7 m2 STANDARD_DEVIATION 0.24 | 1.8 m2 STANDARD_DEVIATION 0.2 | 1.8 m2 STANDARD_DEVIATION 0.2 | 1.8 m2 STANDARD_DEVIATION 0.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 35 Participants | 65 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 161.9 cm STANDARD_DEVIATION 7.01 | 163.9 cm STANDARD_DEVIATION 7.01 | 162.4 cm STANDARD_DEVIATION 6.75 | 162.7 cm STANDARD_DEVIATION 6.88 |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Black or African | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Other, Philippines | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 35 Participants | 31 Participants | 56 Participants | 122 Participants |
| Sex: Female, Male Female | 37 Participants | 35 Participants | 65 Participants | 137 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight (kg) | 71.2 kg STANDARD_DEVIATION 20.52 | 69.9 kg STANDARD_DEVIATION 15.39 | 75.1 kg STANDARD_DEVIATION 17.21 | 72.7 kg STANDARD_DEVIATION 17.76 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 65 | 2 / 37 | 3 / 35 | 11 / 137 |
| other Total, other adverse events | 63 / 65 | 37 / 37 | 35 / 35 | 135 / 137 |
| serious Total, serious adverse events | 15 / 65 | 9 / 37 | 14 / 35 | 38 / 137 |
Outcome results
Primary
Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria
Response rate was calculated per investigator's tumor assessment based on GOG-RECIST, which includes radiographic imaging, physical examination results, and CA-125 levels. No independent review of CT scans (lesion assessments) was performed. CR: disappearance of all target and nontarget lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at baseline, is required for ovarian carcinoma studies. PR is \>= 30% decrease in the sum of LD of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required.
Time frame: GOG-RECIST assessment obtained on cycle2, 4 and 6 Day 21for patients treated with 48 mg/m2 SNS-595 and Day 28 for patients treated with 60 mg/m2, through 28 (±14) days afte the last treatment at the end of safety follow up period
Population: Safety Population which included all patients who received any amount of vosaroxin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 48 mg/m2 | Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria | 7 Participants |
| 60 mg/m2 | Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria | 4 Participants |
| 75 mg/m2 | Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria | 3 Participants |
| Total | Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria | 14 Participants |
Secondary
Progression-free Survival (PFS) Using Kaplan-Meier Methods
PFS is the the time between the date the patient first received Vosaroxin and the earliest date of disease progression. For patients who experienced disease progression, the date of disease progression will be the earliest date on which disease progression is indicated based on the rules. For patients who died with no indication of disease progression, the date of death will be the earliest date on which death is documented based on the rules. For patients who have no indication of disease progression or death, the censoring date will be the Date of Confirmed Contact from the last Survival Follow-Up CRF, or if not in survival follow-up, then the Assessment Date from the last GOG-RECIST CRF, or if no response assessment available, Date of Last Visit / Contact from Extended Treatment Completion CRF if in extended treatment, or from Cycle 6 Completion / Early Termination CRF if not in extended treatment.
Time frame: From the first teratment of Vosaroxin to the end of Cycle 6 or 28 days after the last treatment at the end of safety follow up period if continued in the extended treatment period
Population: Safety population which included all patients who received any amount of vosaroxin
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 48 mg/m2 | Progression-free Survival (PFS) Using Kaplan-Meier Methods | 83 Days |
| 60 mg/m2 | Progression-free Survival (PFS) Using Kaplan-Meier Methods | 61 Days |
| 75 mg/m2 | Progression-free Survival (PFS) Using Kaplan-Meier Methods | 103 Days |
| Total | Progression-free Survival (PFS) Using Kaplan-Meier Methods | 81 Days |