Ovarian Cancer
Conditions
Keywords
ovarian cancer, relapsed ovarian cancer, refractory ovarian cancer
Brief summary
The study is being conducted to find out if paclitaxel works better when given together with an experimental drug called MORAb-003 (farletuzumab) or alone in patients with platinum-resistant or refractory relapsed ovarian cancer
Detailed description
Safety was assessed by the monitoring and recording of all adverse events (AEs), including drug hypersensitivity adverse events (DHAE), and serious adverse events (SAEs); clinical laboratory test (serum chemistry, hematology, urinalysis); tolerability (discontinuations, treatment delays, dose reductions); physical examinations (including vital signs assessment); 12-lead electrocardiograms (ECG) obtained in triplicate and reviewed by independent blinded cardiologist, and Karnofsky's performance status.
Interventions
DRUGMORAb-003 (farletuzumab)
Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.
DRUG0.9% Saline
Placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.
DRUGPaclitaxel
Sponsors
Morphotek
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of non-mucinous epithelial ovarian cancer, including primary peritoneal and fallopian tube malignancies, measurable by CT or MRI scan assessed within 4 weeks prior to study entry * Must have evidence of relapse by CA-125 (2xUpper Limit of Normal) or radiographically within 6 months of most recent platinum-containing chemotherapy. At least one of the lines of chemotherapy must have included a taxane. * Must have been treated with debulking surgery and at least one line platinum-based chemotherapy; * Subjects may have received up to four additional lines of chemotherapy after they developed platinum-resistance. * Subjects must be candidate for repeat paclitaxel treatment
Exclusion criteria
* Clinical contraindications to use of paclitaxel, which include: 1. persistent Grade 2 or greater peripheral neuropathy 2. prior hypersensitivity reaction that persisted despite rechallenge with or without desensitization or resulted in bronchospasm or hemodynamic instability or was at least Grade 2 and resulted in medication discontinuation * Current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas). Note: EOC with prior diagnosis of a low malignant potential tumor that has been surgically resected is acceptable provided the subject did * Prior radiation therapy is excluded with the exception that it is allowable only if measurable disease for ovarian cancer is completely outside the radiation portal * Known allergic reaction to a prior monoclonal antibody therapy or have any documented human anti-human antibody (HAHA). * Previous treatment with MORAb-003 (farletuzumab).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Date of Randomization to date of disease progression or death (whichever came first), assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST), or death regardless of cause. If progression or death was not observed, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier). |
| Overall Survival (OS) | Date of Randomization to date of death, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | OS was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Date of first study drug to disease progression/recurrence, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | BOR was defined as the percentage of participants having either a confirmed complete response (CR) or confirmed partial response (PR) using modified RECIST criteria by independent radiologist review. RECIST criteria was adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Tumor assessments performed up to the initiation of further antitumor treatment were considered. Target lesions selected for response assessment were measured using computed tomography (CT) or magnetic resonance imaging (MRI) scans then graded according to the modified RECIST criteria, adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Participants were assigned to one of the categories of change in disease state; CR, PR, progressive disease (PD), stable disease ( S)D, or not evaluable (NE). |
| Time to Tumor Response (TTR) | Date of Randomization to the first documentation of objective TR, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months | TTR was derived for those participants with objective evidence of CR or PR, and was defined as the time (in months) from the date of randomization to the first documentation of object tumor response (TR). Analysis was based on the Kaplan-Meier estimated percentage of responders. This statistical analysis method measures the effect of study drug on tumor response over a period of time. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Based on Gynecologic Cancer InterGroup (GCIG) | Length of study | Due to termination of the study, data were not collected and the outcome measure for PFS based on GCIG was not analyzed. |
| Serologic Response Rate | Length of study | Due to termination of the study, data were not collected and the outcome measure for Serologic Response Rate was not analyzed. |
Countries
Australia, Belgium, Canada, Netherlands, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MORAb-003 (Farletuzumab) Plus Paclitaxel Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles. Paclitaxel (80 mg/m\^2) was administered weekly by IV infusion over 1 hour following administration of FAR. During the 4-week cycle, Week 4 was to be a rest period with no study treatment (test article or paclitaxel) administered. All participants were required to be premedicated with steroids before paclitaxel administration, and with acetaminophen (650 mg orally) or clinically equivalent per clinic routine within 4 hours prior to test article infusion. | 275 |
| Placebo (Normal Saline) Plus Paclitaxel An equivalent volume of placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles. Paclitaxel (80 mg/m\^2) was administered weekly by IV infusion over 1 hour following administration of FAR. During the 4-week cycle, Week 4 was to be a rest period with no study treatment (test article or paclitaxel) administered. All participants were required to be premedicated with steroids before paclitaxel administration, and with acetaminophen (650 mg orally) or clinically equivalent per clinic routine within 4 hours prior to test article infusion. | 140 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 144 | 68 |
| Overall Study | Discontinuation of study by Sponsor | 123 | 72 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | MORAb-003 (Farletuzumab) Plus Paclitaxel | Placebo (Normal Saline) Plus Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 10.74 | 61.2 Years STANDARD_DEVIATION 9.44 | 61.0 Years STANDARD_DEVIATION 10.31 |
| Sex: Female, Male Female | 275 Participants | 140 Participants | 415 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 278 / 279 | 133 / 133 |
| serious Total, serious adverse events | 127 / 279 | 55 / 133 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier.
Time frame: Date of Randomization to date of death, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Population: ITT population included all participants who were randomly assigned to study drug and analyzed by the treatment assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MORAb-003 (Farletuzumab) Plus Paclitaxel | Overall Survival (OS) | 11.3 Months |
| Placebo (Normal Saline) Plus Paclitaxel | Overall Survival (OS) | 13.1 Months |
p-value: 0.756895% CI: [0.83, 1.48]Log Rank
Primary
Progression-Free Survival (PFS)
PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST), or death regardless of cause. If progression or death was not observed, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier).
Time frame: Date of Randomization to date of disease progression or death (whichever came first), assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Population: Intent-To-Treat (ITT) population included all participants who were randomly assigned to study drug, analyzed by treatment assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MORAb-003 (Farletuzumab) Plus Paclitaxel | Progression-Free Survival (PFS) | 3.5 Months |
| Placebo (Normal Saline) Plus Paclitaxel | Progression-Free Survival (PFS) | 3.7 Months |
p-value: 0.83695% CI: [0.88, 1.46]Log Rank
Secondary
Best Overall Response
BOR was defined as the percentage of participants having either a confirmed complete response (CR) or confirmed partial response (PR) using modified RECIST criteria by independent radiologist review. RECIST criteria was adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Tumor assessments performed up to the initiation of further antitumor treatment were considered. Target lesions selected for response assessment were measured using computed tomography (CT) or magnetic resonance imaging (MRI) scans then graded according to the modified RECIST criteria, adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Participants were assigned to one of the categories of change in disease state; CR, PR, progressive disease (PD), stable disease ( S)D, or not evaluable (NE).
Time frame: Date of first study drug to disease progression/recurrence, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Population: ITT population included all participants who were randomly assigned to study drug and analyzed by the treatment assigned.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MORAb-003 (Farletuzumab) Plus Paclitaxel | Best Overall Response | Complete response (CR) | 0.4 Percentage of participants |
| MORAb-003 (Farletuzumab) Plus Paclitaxel | Best Overall Response | Partial response (PR) | 7.3 Percentage of participants |
| Placebo (Normal Saline) Plus Paclitaxel | Best Overall Response | Complete response (CR) | 0 Percentage of participants |
| Placebo (Normal Saline) Plus Paclitaxel | Best Overall Response | Partial response (PR) | 15.0 Percentage of participants |
p-value: 0.039995% CI: [-14.1, -0.7]Cochran-Mantel-Haenszel
Secondary
Time to Tumor Response (TTR)
TTR was derived for those participants with objective evidence of CR or PR, and was defined as the time (in months) from the date of randomization to the first documentation of object tumor response (TR). Analysis was based on the Kaplan-Meier estimated percentage of responders. This statistical analysis method measures the effect of study drug on tumor response over a period of time.
Time frame: Date of Randomization to the first documentation of objective TR, assessed up to study termination (28 Nov 2011), or up to approximately 2 years 10 months
Population: ITT population (Responders only) included all participants who were randomly assigned to study drug and analyzed by the treatment assigned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MORAb-003 (Farletuzumab) Plus Paclitaxel | Time to Tumor Response (TTR) | 2.0 Months |
| Placebo (Normal Saline) Plus Paclitaxel | Time to Tumor Response (TTR) | 1.7 Months |
Other Pre-specified
Progression Free Survival Based on Gynecologic Cancer InterGroup (GCIG)
Due to termination of the study, data were not collected and the outcome measure for PFS based on GCIG was not analyzed.
Time frame: Length of study
Population: Due to termination of the study, data were not collected and the outcome measure for PFS based on GCIG was not analyzed.
Other Pre-specified
Serologic Response Rate
Due to termination of the study, data were not collected and the outcome measure for Serologic Response Rate was not analyzed.
Time frame: Length of study
Population: Due to termination of the study, data were not collected and the outcome measure for Serologic Response Rate was not analyzed.