Neoplasm, Gastric
Conditions
Brief summary
This is a multicenter, single arm, open-label Phase 1/2 study of pemetrexed plus cisplatin for patients with unresectable, advanced gastric cancer who had no prior palliative chemotherapy. Phase 1 was designed to determine the optimal dose of pemetrexed for its phase 2, which has been completed and now a total of 60 qualified patients will be enrolled in the phase 2 of this study. The treating physician will determined the maximum number of cycles of pemetrexed plus cisplatin that a patient may receive in this study.
Interventions
DRUGpemetrexed
Phase 1 - dose escalating: 600 mg/m2 level 1, 700 mg/m2 level 2, 800 mg/m2 level 3, 900 mg/m2 level 4, intravenous (IV), every 21 days, until disease progression Phase 2 - 700 mg/m2, intravenous (IV), every 21 days, until disease progression
DRUGcisplatin
75 mg/m2, intravenous (IV), every 21 days, until disease progression
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histological proven diagnosis of adenocarcinoma of the stomach * Stage IV disease not amenable to curative surgery. * Disease status must be that of measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. * Performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) scale. * Adequate organ functions
Exclusion criteria
* Prior palliative chemotherapy for advanced gastric cancer. * Pregnancy and breast feeding. * Known or suspected brain metastasis and secondary primary malignancy * Inability to interrupt aspirin, or other non-steroidal anti-inflammatory agents for a 5-day period. * Inability or unwillingness to take folic acid or vitamin B12 supplementation. * Concurrent administration of any other tumor therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Best Tumor Response | baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment) | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | time of response to progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment) | The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. |
| Progression Free Survival | baseline to measured progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment) | The period from study entry until disease progression or death on study, whichever occurred first. |
| Overall Survival | baseline to date of death from any cause (Survival follow-up were performed every 2 cycles during therapy and approximately every 3 months during post-therapy until death or up to 12 months after enrollment) | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. |
Countries
Argentina, Mexico, South Korea, Taiwan
Participant flow
Pre-assignment details
This was a Phase 1/2 trial. There were 16 participants in Phase 1. None of them qualified for the Phase 2 portion of the trial. There were 73 participants in Phase 2; however, 4 were excluded from all analyses due to data quality issues at one site. Results presented here are for the 69 participants in Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Cisplatin Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression | 69 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 33 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Pemetrexed + Cisplatin |
|---|---|
| Age Continuous | 55.9 years STANDARD_DEVIATION 10.2 |
| Eastern Cooperative Oncology Group Performance Status 0 - Fully Active | 42 participants |
| Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 27 participants |
| Race/Ethnicity Caucasian | 1 participants |
| Race/Ethnicity East Asian | 47 participants |
| Race/Ethnicity Hispanic | 21 participants |
| Region of Enrollment Argentina | 18 participants |
| Region of Enrollment Korea, Republic of | 25 participants |
| Region of Enrollment Mexico | 4 participants |
| Region of Enrollment Taiwan | 22 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 69 / — |
| serious Total, serious adverse events | 14 / — |
Outcome results
Primary
Objective Best Tumor Response
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.
Time frame: baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)
Population: All enrolled participants who received at least one dose of study drug. One participant was excluded from analysis because of no measurable disease at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Cisplatin | Objective Best Tumor Response | Partial Response | 15 participants |
| Pemetrexed + Cisplatin | Objective Best Tumor Response | Stable Disease | 22 participants |
| Pemetrexed + Cisplatin | Objective Best Tumor Response | Progressive Disease | 24 participants |
| Pemetrexed + Cisplatin | Objective Best Tumor Response | Unknown | 6 participants |
| Pemetrexed + Cisplatin | Objective Best Tumor Response | Complete Response | 1 participants |
Secondary
Duration of Response
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause.
Time frame: time of response to progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)
Population: All enrolled participants who received at least one dose of study drug, had measureable disease at baseline, and had confirmed complete or partial responses. There were 16 patients qualified for the analysis of duration of response. Twelve participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Duration of Response | 5.4 months |
Secondary
Overall Survival
Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact.
Time frame: baseline to date of death from any cause (Survival follow-up were performed every 2 cycles during therapy and approximately every 3 months during post-therapy until death or up to 12 months after enrollment)
Population: All enrolled participants who received at least one dose of study drug and had measurable disease at baseline. Thirty-five participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Overall Survival | 11.8 months |
Secondary
Progression Free Survival
The period from study entry until disease progression or death on study, whichever occurred first.
Time frame: baseline to measured progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)
Population: All enrolled participants who received at least one dose of study drug and had measureable disease at baseline. Twenty-six participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Progression Free Survival | 4.9 months |