Metastatic Colorectal Cancer
Conditions
Brief summary
A non-randomized phase II study to determine the efficacy and safety of the combination of Pemetrexed and Irinotecan every two weeks in metastatic colorectal cancer patients.
Interventions
DRUGpemetrexed
400 mg/m\^2, intravenous (IV), every 14 days x 12 cycles
DRUGirinotecan
180 mg/m\^2, intravenous (IV), every 14 days x 12 cycles
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of metastatic colorectal adenocarcinoma that is not amenable to curative therapy. * Patient must have at least one unidimensionally measurable lesion. * Prior radiation therapy to less than 25% of bone marrow. Radiation must be completed at least 4 weeks prior to study enrollment. * Performance status 0 to 2 * Patient must have received 1 prior course of chemotherapy (Folfox regimen) for metastatic disease
Exclusion criteria
* Treatment with any drug within the last 30 days that has not received regulatory approval. * Serious systemic disorder (cardiac or pulmonary disease, active infection) * Documented brain metastases not amenable to surgery or unstable after radiation * Inability or unwillingness to take folic acid or Vitamin B12 supplementation. * Presence of fluid retention that can not be controlled by drainage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Tumor Response | baseline to measured progressive disease (up to 2 years follow-up) | Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve (respond), stay the same (stable), or worsen (progression) during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | time of response to progressive disease or death (up to 2 years follow-up) | 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. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve (respond), stay the same (stable), or worsen (progression) during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. |
| Progression-Free Survival (PFS) | baseline to measured progressive disease or death (up to 2 years follow-up) | Defined as the time from study enrollment to the first date of disease progression or death as a result of any cause. PFS was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed. |
| Time to Treatment Failure | baseline to stopping treatment (up to 2 years follow-up) | Defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. |
| Overall Survival | baseline to date of death from any cause (up to 2 years follow-up) | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. |
Countries
France
Participant flow
Pre-assignment details
Two participants discontinued the trial before receiving study treatment. One due to entry criteria exclusion and one due to withdrawal by subject. Therefore, 44 participants received at least one dose of chemotherapy and are included in the efficacy and safety analyses.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Irinotecan Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression | 21 |
| Overall Study | Entry Criteria Exclusion | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Pemetrexed + Irinotecan |
|---|---|
| Age Continuous | 60.8 years STANDARD_DEVIATION 11.5 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active | 24 units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 15 units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 - Ambulatory, No Work Activities | 5 units on a scale |
| Height | 169.3 centimeters STANDARD_DEVIATION 8.5 |
| Pathological Diagnosis Adenocarcinoma of Colon | 22 participants |
| Pathological Diagnosis Adenocarcinoma of Rectum | 20 participants |
| Pathological Diagnosis Colorectal Cancer | 2 participants |
| Region of Enrollment France | 44 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 31 Participants |
| Weight | 69.3 kilograms STANDARD_DEVIATION 11.7 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / — |
| serious Total, serious adverse events | 13 / — |
Outcome results
Primary
Best Overall Tumor Response
Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve (respond), stay the same (stable), or worsen (progression) during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
Time frame: baseline to measured progressive disease (up to 2 years follow-up)
Population: All enrolled participants with at least one completed cycle.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Irinotecan | Best Overall Tumor Response | Progressive Disease | 15 participants |
| Pemetrexed + Irinotecan | Best Overall Tumor Response | Unknown | 5 participants |
| Pemetrexed + Irinotecan | Best Overall Tumor Response | Partial Response | 6 participants |
| Pemetrexed + Irinotecan | Best Overall Tumor Response | Stable Disease | 18 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. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve (respond), stay the same (stable), or worsen (progression) during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Time frame: time of response to progressive disease or death (up to 2 years follow-up)
Population: All enrolled participants with at least completed cycle and who had a complete or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Irinotecan | Duration of Response | 236 days |
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 (up to 2 years follow-up)
Population: All enrolled participants with at least one completed cycle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Irinotecan | Overall Survival | 422 days |
Secondary
Progression-Free Survival (PFS)
Defined as the time from study enrollment to the first date of disease progression or death as a result of any cause. PFS was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed.
Time frame: baseline to measured progressive disease or death (up to 2 years follow-up)
Population: All enrolled participants with at least one completed cycle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Irinotecan | Progression-Free Survival (PFS) | 123 days |
Secondary
Time to Treatment Failure
Defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed.
Time frame: baseline to stopping treatment (up to 2 years follow-up)
Population: All enrolled participants with at least one completed cycle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Irinotecan | Time to Treatment Failure | 66 days |