Gastric Cancer
Conditions
Brief summary
This study will evaluate the disease free survival rate of a combination of capecitabine \[Xeloda\] and oxaliplatin (XELOX) with trastuzumab \[Herceptin\] in patients with resectable gastric cancer. The combination of Xeloda (orally, 1000 mg/m2 on day 1-14 of every cycle) and Herceptin (intravenously, 8 mg/kg loading dose, then 6 mg/kg on days 1-14 of every cycle) will be administered for three cycles prior to surgery to resect the tumor. If complete resection, R0 or microscopic residual tumor R1 is achieved, patients will continue with three cycles of XELOX and Herceptin and then for completion of 12 months treatment with Herceptin alone. Oxaliplatin will be administered intravenously at a dose of 130 mg/m2 on day 1 in every cycle. The anticipated time on study drug will be 12 months.
Interventions
DRUGCapecitabine [Xeloda]
1.000 mg/m2 orally every 12 hours from day 1 to day 14 of every cycle for 6 cycles
DRUGOxaliplatin
130 mg/m2 intravenous infusion day 1 of every cycle
First dose 8 mg/kg, subsequent cycles 6 mg/kg, intravenously, day of every cycle for 15 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
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 over 18 years of age * Locally advanced resectable HER2-positive gastric or esophagogastric junction adenocarcinoma (Sievert types I, II, III) * Measurable (RECIST criteria) or assessable disease * ECOG performance 0-2 * Life expectancy of 12 weeks or more
Exclusion criteria
* Immeasurable lesion as the only evidence of disease * Previous chemotherapy or radiotherapy for gastric neoplasm or some kind of previous surgical resection of the tumor (except diagnostic laparoscopy) * Concomitant heart disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease-free Survival (DFS) at Month 18 | Month 18 | DFS was the time elapsed from the time of surgery (for complete resection \[R0\] participants) until the date on which progression or death from any cause was documented (whichever occured first). Progression was defined as target lesions greater than (\>) 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 millimeter (mm) increase over the nadir. When the sum becomes very small, increases within the measurement error (2-3 mm) can lead to a 20% increase. Participants who did not present progression and who had not died were censored on the last date on which it was known that there was no progression (last response assessment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathological Complete Response (pCR) | Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25 | pCR was defined as an absence of any invasive cancer cell of the primary tumor after the time of major neoadjuvant chemotherapy, with or without surgery. |
| Percentage of Participants With Complete Tumor Resection (R0) | Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25 | R0 resection was defined as having performed a complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation. |
| Percentage of Participants With Objective Response | Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25 | An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR was defined as the disappearance of all target lesions and persistence of greater than or equal to (≥) 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. |
Countries
Spain
Participant flow
Pre-assignment details
Screening period comprised of 35 days. A total of 136 participants were included in the study, of which 36 participants were enrolled and 100 participants discontinued due to screening failures. Abbreviation of AE= adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine+Oxaliplatin+Trastuzumab Participants received 3 cycles of capecitabine (1,000 mg/m\^2 tablet p.o twice daily, Days 1-14)/oxaliplatin (130 mg/m\^2 as a 120-minute IV infusion Day 1 of the cycle)/trastuzumab (8 mg/kg on Day 1, followed by doses of 6 mg/kg as IV infusion) (XELOX-trastuzumab) as neoadjuvant treatment, every 3 weeks, thereafter, they were assessed for surgery. After surgery, participants received 3 cycles of XELOX-trastuzumab as treatment adjuvant to the surgery, thereafter, another 12 cycles of trastuzumab as monotherapy, was administered every 3 weeks, until disease progression or death. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 1 |
| Overall Study | Principal investigator decision | 1 |
| Overall Study | Surgical resection (R2) | 1 |
| Overall Study | Toxicity, AE/intercurrent disease | 7 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Capecitabine+Oxaliplatin+Trastuzumab |
|---|---|
| Age, Continuous | 63.44 years STANDARD_DEVIATION 10.42 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 36 |
| serious Total, serious adverse events | 22 / 36 |
Outcome results
Primary
Percentage of Participants With Disease-free Survival (DFS) at Month 18
DFS was the time elapsed from the time of surgery (for complete resection \[R0\] participants) until the date on which progression or death from any cause was documented (whichever occured first). Progression was defined as target lesions greater than (\>) 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 millimeter (mm) increase over the nadir. When the sum becomes very small, increases within the measurement error (2-3 mm) can lead to a 20% increase. Participants who did not present progression and who had not died were censored on the last date on which it was known that there was no progression (last response assessment).
Time frame: Month 18
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine+Oxaliplatin+Trastuzumab | Percentage of Participants With Disease-free Survival (DFS) at Month 18 | 76.12 percentage of participants |
Secondary
Percentage of Participants With Complete Tumor Resection (R0)
R0 resection was defined as having performed a complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation.
Time frame: Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25
Population: ITT population. Here number of participants analyzed included those who underwent surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine+Oxaliplatin+Trastuzumab | Percentage of Participants With Complete Tumor Resection (R0) | 90.32 percentage of participants |
Secondary
Percentage of Participants With Objective Response
An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR was defined as the disappearance of all target lesions and persistence of greater than or equal to (≥) 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.
Time frame: Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine+Oxaliplatin+Trastuzumab | Percentage of Participants With Objective Response | 38.89 percentage of participants |
Secondary
Percentage of Participants With Pathological Complete Response (pCR)
pCR was defined as an absence of any invasive cancer cell of the primary tumor after the time of major neoadjuvant chemotherapy, with or without surgery.
Time frame: Between Days 7 and 21 of the 3rd cycle of neoadjuvant treatment, thereafter, every 9 weeks during adjuvant treatment and then after adjuvant treatment every 3 months until Month 25
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine+Oxaliplatin+Trastuzumab | Percentage of Participants With Pathological Complete Response (pCR) | 8.33 percentage of participants |