Ovarian Cancer
Conditions
Keywords
Advanced, refractory, or recurrent ovarian cancer
Brief summary
The purpose of this study is to determine if the study drug pertuzumab is effective in treating patients with advanced ovarian cancer that is refractory to, or has recurred following, prior chemotherapy.
Interventions
DRUGPertuzumab (rhuMAb 2C4)
Sponsors
Genentech, Inc.
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Willingness to undergo tumor biopsy and disease that is amenable to biopsy (Cohort 1 only) * Age \>=18 years old * Advanced, histologically documented carcinoma of the ovary * Measurable disease with at least one lesion that can be accurately measured per RECIST in at least one dimension (longest dimension recorded). Each lesion must be \>=20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or \>=10 mm when measured by spiral CT. * Or, clinically or radiologically detectable disease (e.g., ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease). In addition, the subject must have two consecutive pre-treatment CA 125 levels that are both greater than 2× the institutional upper limit of normal (ULN) and \>=40 IU/mL, taken at least 1 week and not more than 3 months apart. The second of the two measurements of CA 125 level should not be drawn within 28 days following the screening biopsy. The later value must be within 2 weeks of starting rhuMAb 2C4 treatment. * One or more prior platinum-based chemotherapeutic regimens for the management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound * Life expectancy \>=12 weeks * ECOG performance status 0 or 1 * Use of an effective means of contraception (for women of childbearing potential) * Granulocyte count \>=1500/uL, platelet count of \>=75,000/uL, and hemoglobin \>=9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin \[Aranesp\] is permitted) * Serum bilirubin \<=1.5× the ULN and alkaline phosphatase, AST, and ALT \<=2.5× ULN (ALT, AST, and alkaline phosphatase \<=5× ULN for subjects with liver metastases) * Serum creatinine \<=1.5× ULN * International normalized ratio (INR) \<1.5 and activated partial thromboplastin time (aPTT) \<1.5 ULN (except for subjects receiving warfarin)
Exclusion criteria
* Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day on which the first rhuMAb 2C4 infusion is administered) * Prior treatment with HER pathway inhibitors (e.g., Herceptin \[Trastuzumab\], Iressa \[gefitinib\], Tarceva \[erlotinib hydrochloride\], C225, CI1033, and TAK165) * History or clinical evidence of central nervous system or brain metastases * Ejection fraction, determined by ECHO, \<50% * Uncontrolled hypercalcemia (\>11.5 mg/dL) * Prior exposure to doxorubicin or liposomal doxorubicin \>360 mg/m2 , mitoxantrone \>120 mg/m2 , or idarubicin \>90 mg/m2 * History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer * History of serious systemic disease, including active infection, uncontrolled hypertension (diastolic blood pressure \>100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible) * Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis * Known human immunodeficiency virus infection * Pregnancy or lactation * Major surgery or significant traumatic injury within 3 weeks prior to Day 1 with the exception of tumor biopsy for the purposes of the study * Inability to comply with study and follow-up procedures * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes | Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab) | Response by tumor measurement occurred if there was documented and confirmed CR or PR determined by 2 consecutive investigator assessments that were at least 28 days apart. Response was assessed by either the RECIST v 1.1 or by CA-125 changes, based on measurable or non-measurable disease at baseline. Per RECIST v 1.1 (for measurable disease), CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Per CA-125 changes (for non-measurable disease), CR: decrease in the CA-125 to within the normal limits and less than (\<) 40 international units per milliliter (IU/mL) and no clinical or radiological evidence of disease, PR: a greater than (\>) 50 percent (%) decrease in CA-125 values from baseline, and no clinical or radiological evidence of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time of PFS | Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab) | PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. |
| Duration of Response | Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab) | Duration of response was defined as the time from the initial CR or PR to the time of disease progression. |
| Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS]) | Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab) | PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. The percentage of participants experiencing disease progression or death was calculated as the number of participants with event divided by the number of participants analyzed, multiplied by 100. |
| Overall Survival | Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years) | 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 Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | 3, 6, and 12 months | Per RECIST v 1.1, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions. |
| Percentage of Participants Who Died | Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years) | The percentage of participants experiencing death was calculated as the number of participants with event divided by the number of participants analyzed, multiplied by 100. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab 420 mg Participants in this group received pertuzumab IV infusion at a loading dose of 840 mg for Cycle 1 (1 Cycle = 3 Weeks), followed by 420 mg for Cycles 2 and beyond, up to 1 year (17 cycles) or until disease progression. | 61 |
| Pertuzumab 1050 mg Participants in this group received 1050 mg of pertuzumab IV infusion at each cycle (1 Cycle = 3 Weeks) up to 1 year (17 cycles) or until disease progression. | 62 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Clinical disease progression | 0 | 4 |
| Overall Study | Died prior to receiving treatment | 4 | 2 |
| Overall Study | Disease progression | 52 | 44 |
| Overall Study | Physician Decision | 2 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Pertuzumab 420 mg | Pertuzumab 1050 mg | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 9.9 | 56.5 years STANDARD_DEVIATION 11.2 | 57.3 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 61 Participants | 62 Participants | 123 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 | 61 / 61 | 60 / 62 |
| serious Total, serious adverse events | 26 / 61 | 18 / 62 |
Outcome results
Primary
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes
Response by tumor measurement occurred if there was documented and confirmed CR or PR determined by 2 consecutive investigator assessments that were at least 28 days apart. Response was assessed by either the RECIST v 1.1 or by CA-125 changes, based on measurable or non-measurable disease at baseline. Per RECIST v 1.1 (for measurable disease), CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Per CA-125 changes (for non-measurable disease), CR: decrease in the CA-125 to within the normal limits and less than (\<) 40 international units per milliliter (IU/mL) and no clinical or radiological evidence of disease, PR: a greater than (\>) 50 percent (%) decrease in CA-125 values from baseline, and no clinical or radiological evidence of new lesions.
Time frame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
Population: Efficacy Analysis Population: All participants who received at least 1 dose of study drug and either underwent at least one postbaseline assessment of response or died within 30 days after the last study treatment before any evaluation of response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 420 mg | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes | 3.6 percentage of participants |
| Pertuzumab 1050 mg | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes | 4.8 percentage of participants |
Secondary
Duration of Response
Duration of response was defined as the time from the initial CR or PR to the time of disease progression.
Time frame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
Population: Only responders (CR or PR) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab 420 mg | Duration of Response | 18.6 weeks |
| Pertuzumab 1050 mg | Duration of Response | 21.1 weeks |
Secondary
Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months
Per RECIST v 1.1, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.
Time frame: 3, 6, and 12 months
Population: Efficacy Analysis Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pertuzumab 420 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 3 months | 25.5 percentage of participants |
| Pertuzumab 420 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 6 months | 7.3 percentage of participants |
| Pertuzumab 420 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 12 months | 0.0 percentage of participants |
| Pertuzumab 1050 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 3 months | 24.2 percentage of participants |
| Pertuzumab 1050 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 6 months | 6.5 percentage of participants |
| Pertuzumab 1050 mg | Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months | % of participants free from PD at 12 months | 0.0 percentage of participants |
Secondary
Median Time of PFS
PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment.
Time frame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
Population: Efficacy Analysis Population. Six participants in pertuzumab 420 mg treatment arm and 15 participants in pertuzumab 1050 mg treatment arm were censored for this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab 420 mg | Median Time of PFS | 7.6 weeks |
| Pertuzumab 1050 mg | Median Time of PFS | 6.1 weeks |
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: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)
Population: Efficacy Analysis Population. Seventeen participants in pertuzumab 420 mg arm and 33 participants in pertuzumab 1050 mg were censored for this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab 420 mg | Overall Survival | 46.7 weeks |
| Pertuzumab 1050 mg | Overall Survival | NA weeks |
Secondary
Percentage of Participants Who Died
The percentage of participants experiencing death was calculated as the number of participants with event divided by the number of participants analyzed, multiplied by 100.
Time frame: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)
Population: Efficacy Analysis Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 420 mg | Percentage of Participants Who Died | 69.1 percentage of participants |
| Pertuzumab 1050 mg | Percentage of Participants Who Died | 46.8 percentage of participants |
Secondary
Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS])
PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. The percentage of participants experiencing disease progression or death was calculated as the number of participants with event divided by the number of participants analyzed, multiplied by 100.
Time frame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
Population: Efficacy Analysis Population. Six participants in pertuzumab 420 mg treatment arm and 15 participants in pertuzumab 1050 mg treatment arm were censored for this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 420 mg | Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS]) | 89.1 percentage of participants |
| Pertuzumab 1050 mg | Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS]) | 75.8 percentage of participants |