Ovarian Cancer
Conditions
Brief summary
This study will evaluate the efficacy and safety of pertuzumab in combination with carboplatin-based standard chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. The anticipated time on study treatment is 3-12 months.
Interventions
DRUGpertuzumab
Loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks
DRUGpaclitaxel
175 mg/m2 IV every 3 weeks for 6 cycles
DRUGgemcitabine
1000 mg/m2 IV Day 1 and 8 of each cycle for 6 cycles
DRUGcarboplatin
Target AUC of 5 following paclitaxel or AUC of 4 following gemcitabine IV every 3 weeks for 6 cycles
Sponsors
Hoffmann-La Roche
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
* histologically confirmed ovarian, primary peritoneal, or fallopian tube cancer; * only 1 previous regimen, which must be platinum-based; * platinum-sensitive disease which is defined by a progression-free interval of greater than 6 months after completion of platinum-based chemotherapy.
Exclusion criteria
* previous radiotherapy; * previous treatment with an anti-cancer vaccine or any targeted therapy; * major surgery or traumatic injury within 4 weeks of study; * history or evidence of central nervous system metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression or Death | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | Disease progression was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors), for participants with measurable disease, or by changes in CA 125 (Cancer Antigen 125) according to GCIG (Gynecologic Cancer Inter Group) for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. |
| Progression-Free Survival | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | Progression-free survival was defined as the time from first administration of study drug (Study Day 1) to documented disease progression or death, whichever occurred earlier. Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. |
| Kaplan-Meier Probability of No Disease or Progression at 1 Year | 1 year | The probability of being event free (no disease progression or death events) at 1 year in participants remaining at risk. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression | Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. |
| Time to Progressive Disease | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression | The time to progressive disease is the interval of time from date of first dose of study medication to date of first documentation of progressive disease by either RECIST or CA 125 criteria. Participants who never progressed while being followed were censored at the last valid tumor measurement or CA 125 measurement. |
| Kaplan-Meier Probability of Being Progression Free at 1 Year | 1 year | — |
| Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks | Response by tumor measurement occurred if there was documented and confirmed complete response (CR) or partial response (PR). For all participants, response was assessed by both the RECIST and by CA 125 levels, according to whether the participant had measurable or non-measurable disease at baseline. Response according to CA 125 levels was defined as at least a 50% reduction from baseline. The decrease had to be confirmed and maintained for at least 28 days. The confirmatory sample must have been less than or equal to the previous sample (within an assay variability of 10%). For overall response, the response categories were response, stable disease and progressive disease. Stable disease included 1) stable disease as defined by RECIST for solid tumors and 2) CA 125 levels that had not met the definition of response or progressive disease. |
| Percentage of Participants Who Died | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | — |
| Overall Survival | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive. |
| Kaplan-Meier Probability of Being Alive at 1 Year | 1 year | — |
| Time To Response | Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment | Time to response was the date of first dose of study medication to the date of the first documentation of response, according to CA 125 criteria for all participants or response according to RECIST criteria for participants with measurable disease. If response was evaluable by both criteria, then the date of response was for the earlier of the two events. |
| Duration of Response | Day 15 of Cycles 2, 4, 6, and Day 15 of all Cycles from Cycle 7 to 17 until disease progression up to 104 weeks | For participants who achieved a response, the duration of response was defined as the interval between initial documentation of response to the first documentation of disease progression or death. Participants who responded and did not progress or die while on study or while being followed were censored at the last valid tumor or CA 125 measurement. |
| Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year | 1 year | — |
Countries
Belgium, Canada, Hungary, Italy, Netherlands, Poland, Russia, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy + Pertuzumab Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles.
Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER: 1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off. | 74 |
| Chemotherapy Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off. | 75 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Lack of Efficacy | 66 | 62 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | Chemotherapy + Pertuzumab | Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 10.16 | 55.3 years STANDARD_DEVIATION 11.41 | 56.7 years STANDARD_DEVIATION 10.86 |
| Sex: Female, Male Female | 74 Participants | 75 Participants | 149 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 | 72 / 75 | 68 / 74 |
| serious Total, serious adverse events | 20 / 75 | 12 / 74 |
Outcome results
Primary
Kaplan-Meier Probability of No Disease or Progression at 1 Year
The probability of being event free (no disease progression or death events) at 1 year in participants remaining at risk.
Time frame: 1 year
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 17 and 12 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Kaplan-Meier Probability of No Disease or Progression at 1 Year | 24 percent |
| Chemotherapy | Kaplan-Meier Probability of No Disease or Progression at 1 Year | 21 percent |
Primary
Percentage of Participants With Disease Progression or Death
Disease progression was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors), for participants with measurable disease, or by changes in CA 125 (Cancer Antigen 125) according to GCIG (Gynecologic Cancer Inter Group) for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks
Population: All treated participants who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Percentage of Participants With Disease Progression or Death | 87.8 percentage of participants |
| Chemotherapy | Percentage of Participants With Disease Progression or Death | 80.0 percentage of participants |
Primary
Progression-Free Survival
Progression-free survival was defined as the time from first administration of study drug (Study Day 1) to documented disease progression or death, whichever occurred earlier. Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Pertuzumab | Progression-Free Survival | 34.1 weeks |
| Chemotherapy | Progression-Free Survival | 40.0 weeks |
p-value: 0.3967Log Rank
p-value: 0.4552Wilcoxon (Mann-Whitney)
p-value: 0.397280% CI: [0.92, 1.49]Wald test
Secondary
Duration of Response
For participants who achieved a response, the duration of response was defined as the interval between initial documentation of response to the first documentation of disease progression or death. Participants who responded and did not progress or die while on study or while being followed were censored at the last valid tumor or CA 125 measurement.
Time frame: Day 15 of Cycles 2, 4, 6, and Day 15 of all Cycles from Cycle 7 to 17 until disease progression up to 104 weeks
Population: Only participants with a response were included in the analysis; 8 participants and 13 participants were censored in the chemotherapy + pertuzumab and chemotherapy only treatment groups, respectively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Pertuzumab | Duration of Response | 28.7 weeks |
| Chemotherapy | Duration of Response | 37.0 weeks |
p-value: 0.3655Log Rank
p-value: 0.1319Wilcoxon (Mann-Whitney)
p-value: 0.367980% CI: [0.92, 1.61]Wald test
Secondary
Kaplan-Meier Probability of Being Alive at 1 Year
Time frame: 1 year
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Kaplan-Meier Probability of Being Alive at 1 Year | 88 percent |
| Chemotherapy | Kaplan-Meier Probability of Being Alive at 1 Year | 85 percent |
Secondary
Kaplan-Meier Probability of Being Progression Free at 1 Year
Time frame: 1 year
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 16 and 10 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Kaplan-Meier Probability of Being Progression Free at 1 Year | 24 percent |
| Chemotherapy | Kaplan-Meier Probability of Being Progression Free at 1 Year | 19 percent |
Secondary
Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year
Time frame: 1 year
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 7 and 5 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year | 18 percent |
| Chemotherapy | Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year | 18 percent |
Secondary
Overall Survival
Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment
Population: All treated participants were included in analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Pertuzumab | Overall Survival | 28.2 months |
| Chemotherapy | Overall Survival | NA months |
p-value: 0.9261Log Rank
p-value: 0.8591Wilcoxon (Mann-Whitney)
p-value: 0.926280% CI: [0.74, 1.41]Wald test
Secondary
Percentage of Participants Who Died
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment
Population: All treated participants were included in analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Percentage of Participants Who Died | 45.9 percentage of participants |
| Chemotherapy | Percentage of Participants Who Died | 41.3 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements
Response by tumor measurement occurred if there was documented and confirmed complete response (CR) or partial response (PR). For all participants, response was assessed by both the RECIST and by CA 125 levels, according to whether the participant had measurable or non-measurable disease at baseline. Response according to CA 125 levels was defined as at least a 50% reduction from baseline. The decrease had to be confirmed and maintained for at least 28 days. The confirmatory sample must have been less than or equal to the previous sample (within an assay variability of 10%). For overall response, the response categories were response, stable disease and progressive disease. Stable disease included 1) stable disease as defined by RECIST for solid tumors and 2) CA 125 levels that had not met the definition of response or progressive disease.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks
Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements | 74.3 percentage of participants |
| Chemotherapy | Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements | 68.0 percentage of participants |
p-value: 0.394380% CI: [-3.9, 16.6]Chi-squared
80% CI: [0.86, 2.17]
Secondary
Percentage of Participants With Disease Progression
Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression
Population: All treated participants were included in analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy + Pertuzumab | Percentage of Participants With Disease Progression | 83.8 percentage of participants |
| Chemotherapy | Percentage of Participants With Disease Progression | 76.0 percentage of participants |
Secondary
Time to Progressive Disease
The time to progressive disease is the interval of time from date of first dose of study medication to date of first documentation of progressive disease by either RECIST or CA 125 criteria. Participants who never progressed while being followed were censored at the last valid tumor measurement or CA 125 measurement.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression
Population: All treated patients with an event (disease progression) were included in analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Pertuzumab | Time to Progressive Disease | 34.3 weeks |
| Chemotherapy | Time to Progressive Disease | 37.3 weeks |
p-value: 0.8129Log Rank
p-value: 0.692Wilcoxon (Mann-Whitney)
p-value: 0.813780% CI: [0.82, 1.32]Wald test
Secondary
Time To Response
Time to response was the date of first dose of study medication to the date of the first documentation of response, according to CA 125 criteria for all participants or response according to RECIST criteria for participants with measurable disease. If response was evaluable by both criteria, then the date of response was for the earlier of the two events.
Time frame: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment
Population: Only participants with a response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Pertuzumab | Time To Response | 6.0 weeks |
| Chemotherapy | Time To Response | 6.3 weeks |
p-value: 0.5726Log Rank
p-value: 0.3903Wilcoxon (Mann-Whitney)
p-value: 0.58780% CI: [0.87, 1.43]Wald test