Epithelial Ovarian Cancer, Primary Peritoneal Carcinoma
Conditions
Brief summary
The purpose of this study is to evaluate the effectiveness and tolerability of the combination of bevacizumab and Abraxane in the treatment of women with epithelial ovarian cancer or peritoneal cancer. The study will also evaluate how the patient's quality of life is during their treatment.
Interventions
DRUGBevacizumab
Bevacizumab will be given via IV infusion at 10mg/kg given on days 1 and 15 of a 28-day cycle.
DRUGAbraxane
Abraxane will be given via IV infusion at 100mg/m²over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Sponsors
Genentech, Inc.
Celgene Corporation
Accelerated Community Oncology Research Network
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Measurable disease by CT or MRI. * At least 1 target lesion to be used to assess response as defined by GOG RECIST criteria. * ECOG performance status of 0 or 1. * Patient provides voluntary written informed consent. * At least 18 years of age. * Negative serum pregnancy test. * Recovered from any recent surgery for at least 30 days and is free of active infection. * Received the following prior therapy at time of enrollment: * Must have had 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or organoplatinum. Initial therapy may have included high-dose therapy, consolidation, or extended therapy. Patient should be defined as recurrent or progression of disease within 6 months of last platinum chemotherapy. * May have had 1 additional cytotoxic or non-cytotoxic chemotherapy regimen. * Must have adequate hematologic and hepatic function.
Exclusion criteria
* Previously received bevacizumab. * History of other invasive malignancy with the exception of nonmelanoma skin cancer. * ECOG performance status of 2, 3, or 4. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study. Patient must be bevacizumab naïve. * Blood pressure of \>150/100 mm Hg on antihypertensive medications. * Prior history of hypertensive crisis or hypertensive encephalopathy. * Diagnosed with unstable angina per NYHA or Grade 2 or greater congestive heart failure. * History of myocardial infarction within 6 months of enrollment. * History of stroke or transient ischemic attack within 6 months prior to study enrollment. * Clinically significant vascular disease (e.g., aortic aneurysm, aortic dissection)or symptomatic peripheral vascular disease. * Bleeding diathesis or coagulopathy. * Presence of CNS or brain metastases. * Pre-existing peripheral neuropathy of Grade ≥ 2. * A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study. * A partial or complete small or large bowel obstruction demonstrated radiologically within 3 months prior to study enrollment. * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment. * Positive pregnancy test or is lactating. * History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to study enrollment. * Serious, non-healing wound, ulcer, or bone fracture. * Serious intercurrent medical or psychiatric illness, including serious active infection. * Inability to comply with study and/or follow-up procedures. * Life expectancy of less than 12 weeks. * Proteinuria at screening as demonstrated by either: * Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR * Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). * Known hypersensitivity to any component of bevacizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression-Free Rate | 6 months after initiation of study treatment | Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months. | Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR. |
| Overall Survival | Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months. | — |
| Progression-free Survival (PFS) | PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months. | Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. |
| Best Overall Response at Six Months | Assessed over 6 months of study treatment | The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR. |
Countries
United States
Participant flow
Recruitment details
9 community oncology research sites across the US within the ACORN network participated in this study. Enrollment started in January 2007 and was completed in December 2008.
Pre-assignment details
Informed consent was obtained from all subjects. All subjects underwent screening procedures to verify eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab and Abraxane All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle. | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient continues on treatment | 1 |
Baseline characteristics
| Characteristic | Bevacizumab and Abraxane |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age Continuous | 61.6 years STANDARD_DEVIATION 10.22 |
| Region of Enrollment United States | 48 participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 48 |
| serious Total, serious adverse events | 13 / 48 |
Outcome results
Primary
6-month Progression-Free Rate
Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Time frame: 6 months after initiation of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Abraxane | 6-month Progression-Free Rate | 62.5 percentage of patients |
Secondary
Best Overall Response
Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.
Time frame: Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab and Abraxane | Best Overall Response | Complete response | 4 Participants |
| Bevacizumab and Abraxane | Best Overall Response | Partial response | 20 Participants |
| Bevacizumab and Abraxane | Best Overall Response | Stable disease | 14 Participants |
| Bevacizumab and Abraxane | Best Overall Response | Progressive disease | 8 Participants |
| Bevacizumab and Abraxane | Best Overall Response | Not evaluable | 2 Participants |
Secondary
Best Overall Response at Six Months
The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.
Time frame: Assessed over 6 months of study treatment
Population: The 2 tailed, 95% confidence interval of the estimated response rate was calculated using the normal approximation to the binomial distribution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab and Abraxane | Best Overall Response at Six Months | 50 percentage of patients |
Secondary
Overall Survival
Time frame: Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months.
Population: Participants who had not experienced death during or after stopping treatment were censored in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab and Abraxane | Overall Survival | 17.15 Months |
Secondary
Progression-free Survival (PFS)
Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Time frame: PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months.
Population: Participants who had not experienced either disease progression or death during or after stopping treatment were censored in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab and Abraxane | Progression-free Survival (PFS) | 8.08 Months |