Gastric Cancer
Conditions
Brief summary
This randomized, multicenter, open-label study will evaluate two different doses of pertuzumab in combination with Herceptin (trastuzumab) and chemotherapy in the first-line treatment of participants with metastatic HER2-positive adenocarcinoma of the stomach or gastroesophageal junction. Participants will be randomized in a 1:1 ratio to two treatment arms. Participants in the Pertuzumab 840/420 mg Arm will receive a pertuzumab loading dose of 840 mg for Cycle 1 and a dose of 420 mg for Cycles 2-6, and participants in the Pertuzumab 840/840 mg Arm will receive pertuzumab 840 mg for all six cycles. Participants in both treatment arms will receive trastuzumab, cisplatin, and capecitabine.
Interventions
DRUGCapecitabine
1000 mg/m2 twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle
DRUGCisplatin
80 mg/m2 on Day 1 of each cycle
DRUGPertuzumab
loading dose of 840 mg, then 420 mg once every three weeks
DRUGTrastuzumab
loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants, greater than or equal to (\>=) 18 of age * Adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy * Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 * HER2-positive tumor * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Life expectancy of at least 3 months
Exclusion criteria
* Previous chemotherapy for advanced or metastatic disease (except (prior adjuvant or neoadjuvant therapy at least 6 months before enrollment in the study) * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * Active (significant or uncontrolled) gastrointestinal bleeding * Abnormal laboratory values
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL) | Day 43 | — |
| Number of Participants With Adverse Events (AEs) | From randomization of first participant to end of study (approximately 6 years) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment. |
Countries
Belgium, Czechia, France, Germany, Italy, Netherlands, South Korea, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab 840/420 mg Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles. | 15 |
| Pertuzumab 840/840 mg Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 10 | 9 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Progression of Disease | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Pertuzumab 840/420 mg | Pertuzumab 840/840 mg | Total |
|---|---|---|---|
| Age, Customized 18 - 40 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized 41 - 64 years | 4 Participants | 9 Participants | 13 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 15 | 9 / 15 |
| other Total, other adverse events | 15 / 15 | 15 / 15 |
| serious Total, serious adverse events | 11 / 15 | 10 / 15 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Time frame: From randomization of first participant to end of study (approximately 6 years)
Population: Safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 840/420 mg | Number of Participants With Adverse Events (AEs) | 15 participants |
| Pertuzumab 840/840 mg | Number of Participants With Adverse Events (AEs) | 15 participants |
Primary
Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL)
Time frame: Day 43
Population: The primary pharmacokinetic (PK) analysis population consisted of all participants with a measurable PK samples on Day 43.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 840/420 mg | Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL) | 91.6 percentage of participants |
| Pertuzumab 840/840 mg | Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL) | 98.3 percentage of participants |