Ovarian Cancer
Conditions
Keywords
ovarian cancer, relapsed ovarian cancer, Platinum-sensitive Ovarian Cancer
Brief summary
This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.
Interventions
DRUGFarletuzumab
Farletuzumab IV infusion.
DRUGCarboplatin
Carboplatin IV infusion.
DRUGTaxane
Taxane (Paclitaxel or Docetaxel) IV infusion.
DRUGFarletuzumab-matched placebo
Farletuzumab-matched placebo IV infusion.
Sponsors
Eisai Europe Ltd. (United Kingdom)
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 No maximum
Healthy volunteers
No
Inclusion criteria
* A histologically or cytologically confirmed diagnosis of non-mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies * Must have measurable disease by CT or MRI scan * Must have relapsed radiologically with a randomization date within ≥6 and \< 24 months of completion of first-line platinum chemotherapy * Have been treated with debulking surgery and first-line platinum and taxane based chemotherapy. * Prior bevacizumbab maintenance is allowed. The last dose of bevacizumab must have been at least 30 days before study Day 1. No cytotoxic maintenance therapy (e.g. taxane) or cancer vaccine therapy is allowed. * Must be a candidate for carboplatin and taxane therapy * Neurologic function: neuropathy (sensory and motor) ≤CTCAE Grade 1
Exclusion criteria
* Subjects who never responded to first-line platinum-based therapy or whose first relapse occurs \<6 months or \>24 months from the last platinum therapy * Subjects who have received other therapy to treat their ovarian cancer since relapse * Known central nervous system (CNS) tumor involvement * Evidence of other active invasive malignancy requiring treatment in the past 5 years * Known allergic reaction to a prior monoclonal antibody therapy or have any documented HAHA * Previous treatment with MORAb-003 (farletuzumab) * Clinical contraindications to use of a taxane
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months) | PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cancer Antigen-125 (CA-125) Progression-Free Survival | From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months) | CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to greater than or equal to (\>=) 2 multiple (\*) ULN with either event documented on two occasions or CA-125 \>=2\*nadir value with either event documented on two occasions. |
| Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria | From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months) | PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart or participants with elevated CA-125 pretreatment, which never normalises must show evidence of CA-125 \>=two times nadir value on two occasions at least one week apart or participants with CA-125 in normal range pretreatment must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart. |
| Percentage of Participants With Length of Second Remission Greater Than First Remission | From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months) | Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defined as the period of time (in months) from the date of completion of platinum-based chemotherapy until the first observation of progression based on GCIG criteria. Based on GCIG criteria, disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. |
| Percentage of Participants With Objective Response | From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months) | Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. |
| Duration of Tumor Response | From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months) | Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR. |
| Time to Tumor Response (TTR) | From the date of randomization to first documentation of objective response (up to 48 months) | Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR. |
| Percentage of Participants With Serologic Response (SR) | Up to 48 months | SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and 75% response definitions, the final sample was analyzed at least 28 days after the previous sample. |
| Duration of 50% Serologic Response | From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months) | Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). |
| Overall Survival (OS) | From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months) | OS was defined as the time (in months) from the date of randomization to the date of death, due to any 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. |
| Percentage of Participants With Clinical Benefit | Up to 48 months | Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions. |
| Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| CL: Clearance of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days) | — |
| Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 3, Cycle 6, Cycle 12 (each cycle length=21 days) | Participant-reported Quality of Life (QoL) was measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O), version 4 and reported in the Treatment Outcome Index (TOI) format. TOI is a 26-item subset of the FACT-O questionnaire composed of the raw sum of the physical well-being subscale (7 items), the functional well-being subscale (7 items), and the ovarian cancer subscale (12 items). Each item was scored on a scale of 0 (not at all) to 4 (very much). Some items were reversed scored. Scores from each subsection were summed into one composite score, termed the FACT-O TOI score which ranged from 0 to 104 and a higher score reflected better QoL. As per planned analysis, farletuzumab treatment groups 1.25 mg/kg and 2.5 mg/kg were pooled for the QoL assessment. |
| Time to 50% Serologic Response (TSR) | From the date of randomization to first documentation of 50% SR (up to 48 months) | TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Philippines, Poland, Portugal, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 274 investigative sites in North America, Europe, Asia Pacific, Latin America, and Japan from 16 April 2009 to 12 April 2013.
Pre-assignment details
A total of 1100 participants were randomized and enrolled, out of which 1091 participants received study treatment. Study was terminated early due to lack of efficacy based on the results for progression-free survival (PFS).
Participants by arm
| Arm | Count |
|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin Participants received farletuzumab 1.25 mg/kg as an IV infusion, weekly followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]) as IV infusion and carboplatin dose to achieve AUC 5 or 6 mg/min/mL (carboplatin dose \[mg\] = Target AUC \[mg\*min/mL\]\*GFR \[mL/min\] + 25), administered as IV infusion on Day 1 of each 21-day cycle for 6 cycles in combination therapy. Following completion of combination therapy, maintenance treatment with farletuzumab 1.25 mg/kg as IV infusion, weekly until disease progression, unacceptable toxicity, intercurrent illness, participant or physician requested discontinuation, or investigator's judgement to discontinue treatment (up to maximum 46 cycles-each cycle 21 days). | 370 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin Participants received farletuzumab 2.5 mg/kg as an IV infusion, weekly followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]) as IV infusion and carboplatin dose to achieve AUC 5 or 6 mg/min/mL (carboplatin dose \[mg\] = Target AUC \[mg\*min/mL\]\*GFR \[mL/min\] + 25), administered as IV infusion on Day 1 of each 21-day cycle for 6 cycles in combination therapy. Following completion of combination therapy, maintenance treatment with farletuzumab 2.5 mg/kg as IV infusion, weekly until disease progression, unacceptable toxicity, intercurrent illness, participant or physician requested discontinuation, or investigator's judgement to discontinue treatment (up to maximum 46 cycles-each cycle 21 days). | 366 |
| Placebo Plus Taxane and Carboplatin Participants received farletuzumab-matched placebo (0.9% saline) as an IV infusion, weekly followed by taxane (paclitaxel \[175 mg/m\^2\] or docetaxel \[75 mg/m\^2\]) as IV infusion and carboplatin dose to achieve AUC 5 or 6 mg/min/mL (carboplatin dose \[mg\] = Target AUC \[mg\*min/mL\]\*GFR \[mL/min\] + 25), administered as IV infusion on Day 1 of each 21-day cycle for 6 cycles in combination therapy. Following completion of combination therapy, maintenance treatment with farletuzumab-matched placebo as IV infusion, weekly until disease progression, unacceptable toxicity, intercurrent illness, participant or physician requested discontinuation, or investigator's judgement to discontinue treatment (up to maximum 46 cycles-each cycle 21 days). | 364 |
| Total | 1,100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Investigator discretion | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 8 | 8 | 8 |
| Overall Study | Other | 18 | 19 | 18 |
| Overall Study | Progressive disease | 119 | 100 | 112 |
| Overall Study | Sponsor decision | 208 | 204 | 190 |
| Overall Study | Withdrawal by Subject | 16 | 33 | 35 |
Baseline characteristics
| Characteristic | 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Placebo Plus Taxane and Carboplatin | Total |
|---|---|---|---|---|
| Age, Continuous | 58.3 Years STANDARD_DEVIATION 10.35 | 58.3 Years STANDARD_DEVIATION 10.26 | 59.0 Years STANDARD_DEVIATION 10.22 | 58.6 Years STANDARD_DEVIATION 10.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 38 Participants | 25 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 331 Participants | 321 Participants | 331 Participants | 983 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 85 Participants | 76 Participants | 86 Participants | 247 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 1 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 7 Participants | 19 Participants |
| Race (NIH/OMB) White | 272 Participants | 271 Participants | 268 Participants | 811 Participants |
| Sex: Female, Male Female | 370 Participants | 366 Participants | 364 Participants | 1100 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 143 / 376 | 119 / 363 | 121 / 352 |
| other Total, other adverse events | 373 / 376 | 358 / 363 | 347 / 352 |
| serious Total, serious adverse events | 140 / 376 | 130 / 363 | 112 / 352 |
Outcome results
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 based on the independent radiologic assessment (modified response evaluation criteria in solid tumors \[RECIST\]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, 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: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Progression-free Survival (PFS) | 9.5 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Progression-free Survival (PFS) | 9.7 months |
| Placebo Plus Taxane and Carboplatin | Progression-free Survival (PFS) | 9.0 months |
p-value: 0.451395% CI: [0.81, 1.21]Log Rank
p-value: 0.076195% CI: [0.7, 1.06]Log Rank
Secondary
AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Here number of participants analyzed signifies participants who were analyzed for this outcome measure for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 58.70 microgram hour per liter (mcg*h/L) | — |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 77.05 microgram hour per liter (mcg*h/L) | Standard Deviation 8.41 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 12.30 microgram hour per liter (mcg*h/L) | Standard Deviation 1.27 |
| Placebo Plus Taxane and Carboplatin | AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 70.37 microgram hour per liter (mcg*h/L) | Standard Deviation 10.4 |
| Placebo Plus Taxane and Carboplatin | AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 16.19 microgram hour per liter (mcg*h/L) | Standard Deviation 6.41 |
Secondary
Cancer Antigen-125 (CA-125) Progression-Free Survival
CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to greater than or equal to (\>=) 2 multiple (\*) ULN with either event documented on two occasions or CA-125 \>=2\*nadir value with either event documented on two occasions.
Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cancer Antigen-125 (CA-125) Progression-Free Survival | 13.2 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cancer Antigen-125 (CA-125) Progression-Free Survival | 18.1 months |
| Placebo Plus Taxane and Carboplatin | Cancer Antigen-125 (CA-125) Progression-Free Survival | 12.0 months |
p-value: 0.293895% CI: [0.72, 1.21]Log Rank
p-value: 0.031895% CI: [0.58, 1.02]Log Rank
Secondary
CL: Clearance of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Here number of participants analyzed signifies participants who were analyzed for this outcome measure for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | CL: Clearance of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 6.65 liter per hour (L/h) | — |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | CL: Clearance of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 8.77 liter per hour (L/h) | Standard Deviation 2.02 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | CL: Clearance of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 24.80 liter per hour (L/h) | Standard Deviation 1.27 |
| Placebo Plus Taxane and Carboplatin | CL: Clearance of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 7.21 liter per hour (L/h) | Standard Deviation 2.4 |
| Placebo Plus Taxane and Carboplatin | CL: Clearance of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 21.00 liter per hour (L/h) | Standard Deviation 11.08 |
Secondary
Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 19.30 microgram per milliliter (mcg/mL) | — |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 3.29 microgram per milliliter (mcg/mL) | — |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 43.55 microgram per milliliter (mcg/mL) | Standard Deviation 22.84 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 3.86 microgram per milliliter (mcg/mL) | Standard Deviation 0.2 |
| Placebo Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 21.72 microgram per milliliter (mcg/mL) | Standard Deviation 12.08 |
| Placebo Plus Taxane and Carboplatin | Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 4.95 microgram per milliliter (mcg/mL) | Standard Deviation 2.73 |
Secondary
Duration of 50% Serologic Response
Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).
Time frame: From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months)
Population: Analysis was performed on a subset of participants who had serologic response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Duration of 50% Serologic Response | 10.7 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Duration of 50% Serologic Response | 12.0 months |
| Placebo Plus Taxane and Carboplatin | Duration of 50% Serologic Response | 9.9 months |
Secondary
Duration of Tumor Response
Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR.
Time frame: From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months)
Population: Analysis performed on a subset of participants who had objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Duration of Tumor Response | 8.0 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Duration of Tumor Response | 8.9 months |
| Placebo Plus Taxane and Carboplatin | Duration of Tumor Response | 7.6 months |
Secondary
Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores
Participant-reported Quality of Life (QoL) was measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O), version 4 and reported in the Treatment Outcome Index (TOI) format. TOI is a 26-item subset of the FACT-O questionnaire composed of the raw sum of the physical well-being subscale (7 items), the functional well-being subscale (7 items), and the ovarian cancer subscale (12 items). Each item was scored on a scale of 0 (not at all) to 4 (very much). Some items were reversed scored. Scores from each subsection were summed into one composite score, termed the FACT-O TOI score which ranged from 0 to 104 and a higher score reflected better QoL. As per planned analysis, farletuzumab treatment groups 1.25 mg/kg and 2.5 mg/kg were pooled for the QoL assessment.
Time frame: Cycle 3, Cycle 6, Cycle 12 (each cycle length=21 days)
Population: The population comprised of all evaluable participants who received at least one dose of farletuzumab or placebo, with study treatment assignment designated according to the IWRS/IVRS, and who completed a baseline FACT-O assessment and at least one follow-up FACT-O assessment during the study. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 3 | 69.6 score on a scale | Standard Deviation 1 |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 6 | 70.1 score on a scale | Standard Deviation 1 |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 12 | 76.2 score on a scale | Standard Deviation 1.7 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 3 | 70.7 score on a scale | Standard Deviation 1.1 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 6 | 70.7 score on a scale | Standard Deviation 1.1 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores | Cycle 12 | 72.9 score on a scale | Standard Deviation 2.4 |
Secondary
Overall Survival (OS)
OS was defined as the time (in months) from the date of randomization to the date of death, due to any 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: From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Overall Survival (OS) | 28.7 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Overall Survival (OS) | 32.1 months |
| Placebo Plus Taxane and Carboplatin | Overall Survival (OS) | 29.1 months |
p-value: 0.482395% CI: [0.78, 1.27]Log Rank
p-value: 0.161695% CI: [0.68, 1.13]Log Rank
Secondary
Percentage of Participants With Clinical Benefit
Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions.
Time frame: Up to 48 months
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Clinical Benefit | 68.9 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Clinical Benefit | 66.4 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Clinical Benefit | 64.6 percentage of participants |
Secondary
Percentage of Participants With Length of Second Remission Greater Than First Remission
Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defined as the period of time (in months) from the date of completion of platinum-based chemotherapy until the first observation of progression based on GCIG criteria. Based on GCIG criteria, disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Time frame: From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS. Here N overall number of participants analyzed included all participants with potential for second remission greater than first remission.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Length of Second Remission Greater Than First Remission | 4.0 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Length of Second Remission Greater Than First Remission | 6.5 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Length of Second Remission Greater Than First Remission | 4.5 percentage of participants |
Secondary
Percentage of Participants With Objective Response
Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Objective Response | 57.6 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Objective Response | 58.2 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Objective Response | 55.8 percentage of participants |
p-value: 0.686495% CI: [-5.4, 9]Cochran-Mantel-Haenszel
p-value: 0.492395% CI: [-4.8, 9.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Serologic Response (SR)
SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and 75% response definitions, the final sample was analyzed at least 28 days after the previous sample.
Time frame: Up to 48 months
Population: SR Evaluable Populations included all randomized participants who received at least one dose of study drug and who had a baseline and at least one assessment during treatment, sufficient to assess the endpoint of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 75% SR (Responder) | 86.1 percentage of participants |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 50% SR (Responder) | 91.9 percentage of participants |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | SR leading to normalization (Responder) | 65.2 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 75% SR (Responder) | 85.7 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 50% SR (Responder) | 97.4 percentage of participants |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | SR leading to normalization (Responder) | 64.8 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 50% SR (Responder) | 92.3 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | SR leading to normalization (Responder) | 59.9 percentage of participants |
| Placebo Plus Taxane and Carboplatin | Percentage of Participants With Serologic Response (SR) | 75% SR (Responder) | 82.0 percentage of participants |
Comparison: 50% serological responsep-value: 0.810695% CI: [-4.9, 4.1]Cochran-Mantel-Haenszel
Comparison: 50% serological responsep-value: 0.006495% CI: [1.4, 8.8]Cochran-Mantel-Haenszel
Comparison: 75% serological responsep-value: 0.300595% CI: [-2, 10.2]Cochran-Mantel-Haenszel
Comparison: 75% serological responsep-value: 0.244595% CI: [-2.5, 9.9]Cochran-Mantel-Haenszel
Comparison: Serologic response leading to normalizationp-value: 0.279795% CI: [-2.8, 13.4]Cochran-Mantel-Haenszel
Comparison: Serologic response leading to normalizationp-value: 0.213695% CI: [-3.2, 13]Cochran-Mantel-Haenszel
Secondary
Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria
PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart or participants with elevated CA-125 pretreatment, which never normalises must show evidence of CA-125 \>=two times nadir value on two occasions at least one week apart or participants with CA-125 in normal range pretreatment must show evidence of CA-125 \>=two times ULN on two occasions at least one week apart.
Time frame: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)
Population: ITT population included all participants randomly assigned to treatment, according to the treatment assigned by the IWRS/IVRS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria | 8.8 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria | 8.6 months |
| Placebo Plus Taxane and Carboplatin | Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria | 8.4 months |
p-value: 0.563695% CI: [0.85, 1.21]Log Rank
p-value: 0.15695% CI: [0.76, 1.09]Log Rank
Secondary
T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Here number of participants analyzed signifies participants who were analyzed for this outcome measure for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 2.94 hours | — |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 1.55 hours | — |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 1.64 hours | Standard Deviation 0.31 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 4.82 hours | Standard Deviation 2.88 |
| Placebo Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 1.72 hours | Standard Deviation 0.65 |
| Placebo Plus Taxane and Carboplatin | T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 4.78 hours | Standard Deviation 3.24 |
Secondary
Time to 50% Serologic Response (TSR)
TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level).
Time frame: From the date of randomization to first documentation of 50% SR (up to 48 months)
Population: Analysis was performed on a subset of participants who had serologic response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Time to 50% Serologic Response (TSR) | 1.0 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Time to 50% Serologic Response (TSR) | 0.9 months |
| Placebo Plus Taxane and Carboplatin | Time to 50% Serologic Response (TSR) | 1.2 months |
Secondary
Time to Tumor Response (TTR)
Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR.
Time frame: From the date of randomization to first documentation of objective response (up to 48 months)
Population: Analysis performed on a subset of participants who had objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Time to Tumor Response (TTR) | 1.5 months |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Time to Tumor Response (TTR) | 1.5 months |
| Placebo Plus Taxane and Carboplatin | Time to Tumor Response (TTR) | 1.5 months |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 0.75 hours |
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 3.00 hours |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 0.79 hours |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 3.21 hours |
| Placebo Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 1.96 hours |
| Placebo Plus Taxane and Carboplatin | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 3.00 hours |
Secondary
Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel
Time frame: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)
Population: Pharmacokinetic Analysis Set included all participants who have sufficient pharmacokinetic data to derive at least one pharmacokinetic parameter. Pharmacokinetic data was collected and analyzed only for a maximum of 7 participants in this study. Here overall number of participants analyzed signifies participants who were analyzed for this outcome measure. Here number of participants analyzed signifies participants who were analyzed for this outcome measure for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin | Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 28.20 liter | — |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 20.30 liter | Standard Deviation 0.85 |
| 2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin | Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 169.50 liter | Standard Deviation 94.05 |
| Placebo Plus Taxane and Carboplatin | Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Total Carboplatin | 14.86 liter | Standard Deviation 5.51 |
| Placebo Plus Taxane and Carboplatin | Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel | Total Paclitaxel | 110.23 liter | Standard Deviation 52.34 |