Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to assess the efficacy and toxicity of pemetrexed dosing that is tailored to individual patient tolerance in patients with advanced non-small cell lung cancer (NSCLC).
Interventions
DRUGpemetrexed
500 milligrams per square meter (mg/m2), intravenous (IV) in the first cycle. Acceptable toxicity\* in cycle 1 determines dose increase to 1000 mg/m2 or dose decrease to 375 mg/m2 with unacceptable toxicity every 3 week in subsequent cycles till progression of disease. \*Toxicity acceptable if none of the following toxicities recorded at any time during Cycle 1: Platelets \<50 x 10\^9/L; absolute neutrophil count \<1.0 x 10\^9/L; Stomatitis/pharyngitis/esophagitis/diarrhea Grade \>2; Skin Grade \>2; Serum bilirubin \>3.0 x upper limit of normal (ULN); alanine aminotransferase/aspartate aminotransferase \>10 x ULN; Other non-hematologic toxicities Grade \>2 (except nausea, vomiting).
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
* Histologic or cytologic diagnosis non-small cell lung cancer (NSCLC) (Stage IIIB or IV) * Patients' NSCLC must have progressed following one chemotherapy regimen for palliative therapy with or without subsequent targeted biological therapy * Disease status must be that of measureable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Exclusion criteria
* Concurrent administration of any other tumor therapy * Pregnancy or breast feeding * Serious concomitant disorders * Inability or unwillingness to take folic acid or vitamin B12 supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) | baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | The objective response rate (ORR) was defined as the proportion of participants who achieved a best response of either complete response (CR) or partial response (PR) (responders) based on the RECIST criteria. ORR=(CR+PR)/Number of Participants. The RECIST define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | baseline to date of death from any cause (includes post-treatment follow-up of up to 18 months post-Last Patient Entered Treatment) | Overall survival is the duration from enrollment to death from any cause. For patients who are alive, overall survival is censored at the last follow-up visit. |
| Progression-Free Survival (PFS) | baseline to measured progressive disease or death from any cause (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | Time to PFS was defined as the time from the date of enrollment to the date of the first of the following events: objective disease progression or death due to any cause. Survival time frame includes post-treatment follow-up of up to 18 months post-Last Patient Entered Treatment. Patients were censored if their disease had not progressed, treatment was discontinued due to an undocumented progression or toxicity/other reason, onset of new anti-tumor therapy or otherwise experienced death/progression after more than one missed (assessment) visit. |
| Proportion of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | DCR was defined as the proportion of best overall response of CR, PR, and SD. DCR=(CR+PR+SD)/Number of participants. Response was evaluated 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; Stable Disease=small changes that do not meet above criteria. |
| Time to Treatment Failure | baseline to early treatment discontinuation or measured progressive disease or death from any cause (assessments every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | Time to treatment failure was define as the time from the date of enrollment to the date of the first of the following events: objective disease progression, death due to any cause, treatment discontinuation for undocumented progression, early treatment discontinuation for toxicity or other reason, or new anticancer treatment started. Time to treatment failure for participants who were still participating in the study without treatment failure at the time of analysis were treated as censored at the date of the last tumor assessment. |
| Time to Tumor Progression | baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | Time to documented tumor progression was defined as the time from the date of enrollment to the first date of documented disease progression. Time to documented disease progression was censored at the date of death for participants who had not had documented disease progression. Otherwise, the censoring rules were the same as for Progression-Free Survival. |
| Duration of Response | time of response to measured progressive disease or death from any cause (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment) | Duration of overall tumor response was measured from the time of first documentation of complete response or partial response (whichever status was first recorded) until the date of progression-free survival, with censoring defined as: disease had not progressed, treatment was discontinued due to undocumented progression or toxicity/other reason, onset of new anti-tumor therapy or otherwise experienced death/progression after more than one missed (assessment) visit. |
Countries
Taiwan
Participant flow
Pre-assignment details
Thirty-seven participants were screened; 3 did not meet inclusion/exclusion criteria and one withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed 500 milligrams per square meter (mg/m2), intravenous (IV), every 21 days until disease progression (toxicity in cycle 1 determines dose increase to 1000 mg/m2 or dose decrease to 375 mg/m2 in subsequent cycles). | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death after 30-day post-therapy followup | 17 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| 24 Hour Creatinine Clearance | 81.142 milliliters per minute (ml/min) STANDARD_DEVIATION 24.9265 |
| Age Continuous | 58.0 years STANDARD_DEVIATION 11.27 |
| Body Temperature | 36.25 degrees Celcius (°C) STANDARD_DEVIATION 0.336 |
| Disease Characteristic: Basis for Diagnosis Cytological | 16 participants |
| Disease Characteristic: Basis for Diagnosis Histopathological | 17 participants |
| Disease Characteristic: Disease Stage at Study Entry Stage IIIB | 3 participants |
| Disease Characteristic: Disease Stage at Study Entry Stage IV | 30 participants |
| Disease Characteristic: Eastern Cooperative Oncology Group Performance Status 0 - Fully Active | 9 participants |
| Disease Characteristic: Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 24 participants |
| Disease Characteristic: Time from Initial Diagnosis to Prior Chemotherapy Failure | 12.04 months STANDARD_DEVIATION 23.764 |
| Disease Characteristic: Time from Initial Diagnosis to Study Entry | 11.54 months STANDARD_DEVIATION 20.829 |
| Disease Characteristic: Time from Prior Chemotherapy Failure to Study Entry | 1.00 months STANDARD_DEVIATION 0.486 |
| Disease Characterstic: Pathological Diagnosis Code Adenocarcinoma of Lung | 23 participants |
| Disease Characterstic: Pathological Diagnosis Code Large Cell Carcinoma of Lung | 1 participants |
| Disease Characterstic: Pathological Diagnosis Code Mixed Cell | 0 participants |
| Disease Characterstic: Pathological Diagnosis Code Non-Small Cell Lung Carcinoma | 1 participants |
| Disease Characterstic: Pathological Diagnosis Code Squamous Cell Carcinoma of Lung | 8 participants |
| Heart Rate | 87.5 beats per minute (bpm) STANDARD_DEVIATION 15 |
| Height | 162.0 centimeters STANDARD_DEVIATION 8.59 |
| Homocysteine | 7.521 micromoles per Liter (μmol/L) STANDARD_DEVIATION 2.6229 |
| Race/Ethnicity East/Southeast Asian | 33 participants |
| Region of Enrollment Taiwan | 33 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 20 Participants |
| Smoking Status Ever Smoking | 20 participants |
| Smoking Status Never Smoking | 13 participants |
| Weight | 63.08 kilograms STANDARD_DEVIATION 9.912 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 13 / 33 |
Outcome results
Primary
Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
The objective response rate (ORR) was defined as the proportion of participants who achieved a best response of either complete response (CR) or partial response (PR) (responders) based on the RECIST criteria. ORR=(CR+PR)/Number of Participants. The RECIST define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatments.
Time frame: baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment)
Population: Number of participants who received at least one dose of study drug. Participants who were classified as Unknown were considered nonresponders rather than missing.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed | Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) | 0.182 proportion of responders |
Secondary
Duration of Response
Duration of overall tumor response was measured from the time of first documentation of complete response or partial response (whichever status was first recorded) until the date of progression-free survival, with censoring defined as: disease had not progressed, treatment was discontinued due to undocumented progression or toxicity/other reason, onset of new anti-tumor therapy or otherwise experienced death/progression after more than one missed (assessment) visit.
Time frame: time of response to measured progressive disease or death from any cause (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment)
Population: Participants who received study drug and who had either a complete or partial response to treatment. Three participants were censored as they were alive at the time of analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Duration of Response | 6.6 months |
Secondary
Overall Survival
Overall survival is the duration from enrollment to death from any cause. For patients who are alive, overall survival is censored at the last follow-up visit.
Time frame: baseline to date of death from any cause (includes post-treatment follow-up of up to 18 months post-Last Patient Entered Treatment)
Population: Number of participants who received at least one dose of study drug. Sixteen participants were censored as they were alive at the time of analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Overall Survival | 20.2 months |
Secondary
Progression-Free Survival (PFS)
Time to PFS was defined as the time from the date of enrollment to the date of the first of the following events: objective disease progression or death due to any cause. Survival time frame includes post-treatment follow-up of up to 18 months post-Last Patient Entered Treatment. Patients were censored if their disease had not progressed, treatment was discontinued due to an undocumented progression or toxicity/other reason, onset of new anti-tumor therapy or otherwise experienced death/progression after more than one missed (assessment) visit.
Time frame: baseline to measured progressive disease or death from any cause (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment)
Population: Number of participants who received at least one dose of study drug. Sixteen participants were censored as they were alive at the time of analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Progression-Free Survival (PFS) | 6.9 months |
Secondary
Proportion of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR])
DCR was defined as the proportion of best overall response of CR, PR, and SD. DCR=(CR+PR+SD)/Number of participants. Response was evaluated 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; 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 documented disease progression, or up to 18 months after enrollment)
Population: Number of participants who received at least one dose of study drug. Participants who were classified as Unknown were considered nonresponders rather than missing.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed | Proportion of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate [DCR]) | 0.545 proportion of participants |
Secondary
Time to Treatment Failure
Time to treatment failure was define as the time from the date of enrollment to the date of the first of the following events: objective disease progression, death due to any cause, treatment discontinuation for undocumented progression, early treatment discontinuation for toxicity or other reason, or new anticancer treatment started. Time to treatment failure for participants who were still participating in the study without treatment failure at the time of analysis were treated as censored at the date of the last tumor assessment.
Time frame: baseline to early treatment discontinuation or measured progressive disease or death from any cause (assessments every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment)
Population: Number of participants who received at least one dose of study drug. One patient was censored as he/she was alive at time of analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Time to Treatment Failure | 2.9 months |
Secondary
Time to Tumor Progression
Time to documented tumor progression was defined as the time from the date of enrollment to the first date of documented disease progression. Time to documented disease progression was censored at the date of death for participants who had not had documented disease progression. Otherwise, the censoring rules were the same as for Progression-Free Survival.
Time frame: baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until documented disease progression, or up to 18 months after enrollment)
Population: Number of participants who received at least one dose of study drug. Sixteen participants were censored as they were alive at the time of analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Time to Tumor Progression | 6.9 months |