Gastric Cancer
Conditions
Brief summary
This open-label, multi-center study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with standard chemotherapy as first-line treatment in patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Patients will receive standard chemotherapy for a maximum of 6 cycles, and 8 mg/kg Herceptin as loading dose on day 1, followed by 6 mg/kg intravenous infusion every 3 weeks until disease progression.
Interventions
Loading dose of 8 mg/kg on day 1, followed by 6 mg/kg intravenous infusion every 3 weeks until disease progression in combination with standard chemotherapy
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with advanced or metastatic disease, not amenable to curative therapy * Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) * HER2 positive tumor (primary tumor or metastasis * ECOG Performance status 0, 1 or 2 * Life expectancy of at least 3 months
Exclusion criteria
* Previous chemotherapy for advanced or metastatic disease less than 6 month before study start * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (patients with partial or total gastrectomy are allowed to participate in the study) * Patients with active (significant or uncontrolled) gastrointestinal bleeding * Residual relevant toxicity resulting from previous chemotherapy * Other malignancy within the last 5 years (except carcinoma in situ of the cervix, or basal cell carcinoma)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) | Baseline up to PD or death (maximum up to 22 months) | The PFS was defined as the median time between the day of enrollment and the first documentation of progressive disease (PD) or date of death, whichever occurred first. PD was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters \[mm\]) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. The censoring date was the last date of last tumor measurement, last date of study drug treatment, or last follow-up. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Tumor Response | Baseline up to PD or death (maximum up to 22 months) | Overall tumor response was defined as the occurrence of either a confirmed complete response (CR) or a partial response (PR) as best overall response as determined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1 from confirmed radio-graphic evaluations of target and non-target lesions. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than \[\<\]10 mm); no new lesions. PR was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions. |
| Percentage of Participants With Clinical Benefit Response (CBR) | Baseline up to PD or death (maximum up to 22 months) | CBR was defined as any response among stable disease (SD) for 6 weeks or longer, CR, or PR as determined by the RECIST v 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. SD was defined as not qualifying for CR, PR, or PD. |
| Duration of Response (DR) | Baseline up to PD or death (maximum up to 22 months) | DR was based on RECIST criteria v1.1 and was defined as time from date the CR or PR was first recorded to the date on which PD was first noted. CR: complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR: \>=30% decrease under baseline of the sum of diameters of all target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions and/or appearance of 1 or more new lesions. For the participants with no documented progression after CR or PR, the censored date (the date of death, the last tumor measurement, last date in drug log, or last follow-up) was taken into consideration. The median duration of response with 95% CI was estimated using Kaplan Meier method. |
| Overall Survival (OS) | Baseline up to death (maximum up to 22 months) | OS was defined as the time from the date of enrollment to the date of the death (from any cause). If no death was observed, censored observations were taken into account in the analysis. The censoring date was the last date of last tumor measurement, last date in drug log, or last follow-up. The median overall survival time with 95% CI was estimated using Kaplan Meier method. |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Baseline up to 6 month after last dose of study drug (maximum up to 22 months) | Lab parameters assessed during the study were serum chemistry, biochemistry - serum electrolytes, hematology, 12 lead electrocardiogram, and urinalysis - protein, glucose, blood and other lab tests. Laboratory tests were graded according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) version 3. |
| Number of Participants With Clinically Significant Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Baseline, thereafter every 12 weeks (maximum up to 22 months) | The LVEF was measured using Multi Gated Acquisition (MUGA) or echocardiography (echocardiography was preferred), using the same technique throughout for consistency in an individual participant. Baseline LVEF assessments were done within 21 days prior to the start of treatment. Participants with clinically significant change from baseline (that is, absolute drop in LVEF of \>=15%, and drop to a value \<50%) have been reported. |
| Number of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Gastric Cancer | Baseline | The HER2 status was determination by using immunohistochemistry (IHC) and confirmatory Fluorescent In Situ Hybridization (FISH) techniques. Only participants with HER2 positivity were allowed to receive study medication. |
| Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 6 month after last dose of study drug (maximum up to 22 months) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious AEs. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Trastuzumab was administered at a loading dose of 8 mg/kg on Day 1, followed by 6 mg/kg intravenous infusion every 3 weeks plus standard chemotherapy as per Investigator's discretion or as per institutional practice, until disease progression, early withdrawal due to unmanageable toxicity, or consent withdrawal. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal of Consent | 1 |
Baseline characteristics
| Characteristic | Trastuzumab |
|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 7.27 |
| Gender Female | 1 Participants |
| Gender Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Median Progression Free Survival (PFS)
The PFS was defined as the median time between the day of enrollment and the first documentation of progressive disease (PD) or date of death, whichever occurred first. PD was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters \[mm\]) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. The censoring date was the last date of last tumor measurement, last date of study drug treatment, or last follow-up. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method.
Time frame: Baseline up to PD or death (maximum up to 22 months)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Median Progression Free Survival (PFS) | 254.0 days |
Secondary
Duration of Response (DR)
DR was based on RECIST criteria v1.1 and was defined as time from date the CR or PR was first recorded to the date on which PD was first noted. CR: complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR: \>=30% decrease under baseline of the sum of diameters of all target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions and/or appearance of 1 or more new lesions. For the participants with no documented progression after CR or PR, the censored date (the date of death, the last tumor measurement, last date in drug log, or last follow-up) was taken into consideration. The median duration of response with 95% CI was estimated using Kaplan Meier method.
Time frame: Baseline up to PD or death (maximum up to 22 months)
Population: ITT population. The number of participants analyzed signifies the number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Duration of Response (DR) | NA days |
Secondary
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious AEs.
Time frame: Baseline up to 6 month after last dose of study drug (maximum up to 22 months)
Population: Safety population included all participants who had received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 4 participants |
| Trastuzumab | Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 2 participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
Lab parameters assessed during the study were serum chemistry, biochemistry - serum electrolytes, hematology, 12 lead electrocardiogram, and urinalysis - protein, glucose, blood and other lab tests. Laboratory tests were graded according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) version 3.
Time frame: Baseline up to 6 month after last dose of study drug (maximum up to 22 months)
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | 0 participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
The LVEF was measured using Multi Gated Acquisition (MUGA) or echocardiography (echocardiography was preferred), using the same technique throughout for consistency in an individual participant. Baseline LVEF assessments were done within 21 days prior to the start of treatment. Participants with clinically significant change from baseline (that is, absolute drop in LVEF of \>=15%, and drop to a value \<50%) have been reported.
Time frame: Baseline, thereafter every 12 weeks (maximum up to 22 months)
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Number of Participants With Clinically Significant Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | 0 participants |
Secondary
Number of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Gastric Cancer
The HER2 status was determination by using immunohistochemistry (IHC) and confirmatory Fluorescent In Situ Hybridization (FISH) techniques. Only participants with HER2 positivity were allowed to receive study medication.
Time frame: Baseline
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Number of Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Gastric Cancer | 4 participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of enrollment to the date of the death (from any cause). If no death was observed, censored observations were taken into account in the analysis. The censoring date was the last date of last tumor measurement, last date in drug log, or last follow-up. The median overall survival time with 95% CI was estimated using Kaplan Meier method.
Time frame: Baseline up to death (maximum up to 22 months)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Overall Survival (OS) | 508.0 days |
Secondary
Percentage of Participants With Clinical Benefit Response (CBR)
CBR was defined as any response among stable disease (SD) for 6 weeks or longer, CR, or PR as determined by the RECIST v 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis \<10 mm); no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. SD was defined as not qualifying for CR, PR, or PD.
Time frame: Baseline up to PD or death (maximum up to 22 months)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Percentage of Participants With Clinical Benefit Response (CBR) | 75.0 percentage of participants |
Secondary
Percentage of Participants With Overall Tumor Response
Overall tumor response was defined as the occurrence of either a confirmed complete response (CR) or a partial response (PR) as best overall response as determined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1 from confirmed radio-graphic evaluations of target and non-target lesions. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than \[\<\]10 mm); no new lesions. PR was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions (the short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions); no unequivocal progression of non-target disease; no new lesions.
Time frame: Baseline up to PD or death (maximum up to 22 months)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Percentage of Participants With Overall Tumor Response | 50 percentage of participants |