Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Conditions
Keywords
Omnitarg, Cancer, Platinum-Resistant
Brief summary
This is a Phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial of pertuzumab in combination with gemcitabine relative to placebo in combination with gemcitabine in subjects with advanced ovarian, primary peritoneal, or fallopian tube cancer that is resistant to platinum-based chemotherapy.
Interventions
DRUGPlacebo
Placebo was provided as a single-use formulation for infusion.
DRUGGemcitabine
Gemcitabine was provided as a solution for infusion.
DRUGPertuzumab
Pertuzumab was provided as a single-use formulation for infusion.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Age \>= 18 years * Advanced, histologically documented ovarian, primary peritoneal, or fallopian tube carcinoma * Representative tumor specimens in paraffin blocks or at least 12 unstained slides with an associated pathology report, obtained at any time prior to entry of study for evaluation of HER2 activation * Measurable disease with at least one lesion that can be accurately measured in at least one dimension (longest dimension recorded), Or: * Clinically or radiologically detectable disease (e.g., ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease) * Platinum-resistant or refractory carcinoma * Life expectancy \>= 12 weeks * ECOG performance status 0 or 1 * LVEF \>= 50%, as determined by ECHO * Use of an effective means of contraception (for women of childbearing potential) * Clinical laboratory test results: Granulocyte count \>= 1500/uL; Platelet count \>= 75,000/uL; Hemoglobin \>= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin \[Aranesp(R)\] is permitted); Serum bilirubin \<= 1.5 the ULN; Alkaline phosphatase, AST, and ALT \<= 2.5 ULN (AST, ALT \<= 5 ULN for subjects with liver metastasis); Serum creatinine \<= 1.5 ULN; International normalized ratio (INR) \<= 1.5 and activated partial thromboplastin time (aPTT) \<= 1.5 ULN (except for subjects receiving anti-coagulation therapy)
Exclusion criteria
* Prior treatment with gemcitabine * Two or more prior regimens for the treatment of platinum-resistant disease * Two or more non-platinum-containing regimens for the treatment of platinum-sensitive disease * Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day the first study treatment infusions are administered) * Prior treatment with HER2 pathway inhibitors (e.g., Herceptin(R) \[trastuzumab\], Iressa(R) \[gefitinib\], Tarceva\<TM\> \[erlotinib hydrochloride\], cetuximab, GW572016) * History or clinical evidence of central nervous system or brain metastases * Uncontrolled hypercalcemia ( \> 11.5 mg/dL) * Prior exposure of \> 360 mg/m\^2 doxorubicin or liposomal doxorubicin, \> 120 mg/m\^2 mitoxantrone, or \> 90 mg/m\^2 idarubicin * History of other malignancies within 5 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, basal or squamous cell skin cancer * History of serious systemic disease, unstable angina, myocardial infarction within 6 months prior to Day 1 of treatment, symptoms of CHF, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia \[i.e., atrial fibrillation, paroxysmal supraventricular tachycardia\] are eligible) * Known HIV infection * Pregnancy or lactation * Major surgery or significant traumatic injury within 3 weeks prior to Day 1 of treatment * 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 |
|---|---|---|
| Progression-free Survival | Baseline to the end of the study (up to 1 year) | Progression-free survival was defined as the time from the first day of treatment (Cycle 1, Day 1) to the time of documented disease progression or death, whichever occurred first. Disease progression was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Objective Response | Baseline to the end of the study (up to 1 year) | An objective response was defined as a complete or partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors (RECIST). A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions. |
| Duration of the Objective Response | Baseline to the end of the study (up to 1 year) | Duration of the objective response was defined as the time from the initial response to disease progression or death from any cause. |
| Percentage of Participants Free From Disease Progression at 4 Months | Baseline to Month 4 | 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 of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Duration of Survival | Baseline to the end of the study (up to 1 year) | Duration of survival was defined as the time from randomization until death from any cause. |
Countries
United States
Participant flow
Pre-assignment details
One subject in the placebo + gemcitabine arm did not receive any study treatment as the subject died of a cerebrovascular accident prior to the first scheduled dose. This subject was excluded from both the efficacy and safety analyses, per protocol.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Gemcitabine Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles).
Placebo: Placebo was provided as a single-use formulation for infusion.
Gemcitabine: Gemcitabine was provided as a solution for infusion. | 65 |
| Pertuzumab + Gemcitabine Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles
Gemcitabine: Gemcitabine was provided as a solution for infusion.
Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion. | 65 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 8 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease progression | 56 | 53 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Other unspecified | 1 | 1 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Subject's decision | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo + Gemcitabine | Pertuzumab + Gemcitabine | Total |
|---|---|---|---|
| Age, Continuous | 59.7 years STANDARD_DEVIATION 11.94 | 57.8 years STANDARD_DEVIATION 10.79 | 58.7 years STANDARD_DEVIATION 11.38 |
| Sex: Female, Male Female | 65 Participants | 65 Participants | 130 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 | 65 / 65 | 65 / 65 |
| serious Total, serious adverse events | 40 / 65 | 23 / 65 |
Outcome results
Primary
Progression-free Survival
Progression-free survival was defined as the time from the first day of treatment (Cycle 1, Day 1) to the time of documented disease progression or death, whichever occurred first. Disease progression was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Gemcitabine | Progression-free Survival | 2.6 months |
| Pertuzumab + Gemcitabine | Progression-free Survival | 2.9 months |
Secondary
Duration of Survival
Duration of survival was defined as the time from randomization until death from any cause.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Gemcitabine | Duration of Survival | 13.1 months |
| Pertuzumab + Gemcitabine | Duration of Survival | 13.0 months |
Secondary
Duration of the Objective Response
Duration of the objective response was defined as the time from the initial response to disease progression or death from any cause.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication. Only participants with an objective response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Gemcitabine | Duration of the Objective Response | NA months |
| Pertuzumab + Gemcitabine | Duration of the Objective Response | 6.9 months |
Secondary
Percentage of Participants Free From Disease Progression at 4 Months
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 of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Baseline to Month 4
Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Gemcitabine | Percentage of Participants Free From Disease Progression at 4 Months | 37.3 percentage of participants |
| Pertuzumab + Gemcitabine | Percentage of Participants Free From Disease Progression at 4 Months | 47.6 percentage of participants |
Secondary
Percentage of Participants With an Objective Response
An objective response was defined as a complete or partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors (RECIST). A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Gemcitabine | Percentage of Participants With an Objective Response | 4.6 percentage of participants |
| Pertuzumab + Gemcitabine | Percentage of Participants With an Objective Response | 13.8 percentage of participants |