Non Small Cell Lung Cancer
Conditions
Brief summary
Chemotherapy for patients with non-squamous non-small cell lung cancer. Patients are given folic acid, vitamin B12 and steroids, both before and during treatment, to reduce the side effects associated with pemetrexed. The aim is whether it is possible to simplify the folic acid and steroid schedule without increasing toxicity.
Interventions
DRUGpemetrexed
500 mg/m\^2 intravenous infusion on day 1 of each 21-day cycle. Number of Cycles: Until progression or to a maximum of 6 cycles.
DIETARY_SUPPLEMENTFolic acid
350-1000 micrograms taken orally for at least 5 daily doses during the 7-day period prior to the first dose of pemetrexed then continues daily throughout treatment until 3 weeks after the last dose of pemetrexed.
DIETARY_SUPPLEMENTFolic Acid
350-1000 micrograms taken orally for two consecutive daily doses of folic acid the day before and the day of the first dose of pemetrexed the continues throughout treatment and for 3 weeks after the last dose of pemetrexed.
DIETARY_SUPPLEMENTVitamin B12
1000 micrograms intramuscular injection of vitamin B12 during the week prior to the first dose of pemetrexed then further injections given approximately every 9 weeks until 3 weeks after the last dose of pemetrexed.
DRUGdexamethasone
4 mg taken orally \[or equivalent\] twice per day the day before, the day of, and the day after the first day of pemetrexed. Continue to give dexamethasone twice per day the day before, the day of, and the day after each dose of pemetrexed.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC) with locally advanced or metastatic disease (Stage IIIA, IIIB or IV)that is of non-squamous histology * Patients must have failed only one prior chemotherapy regime and must be considered eligible for further chemotherapy following progression of their disease. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Adequate organ function
Exclusion criteria
* Concurrent administration of any other anti-tumor therapy * Other co-existing malignancies * 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 |
|---|---|---|
| Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity | From first dose of treatment to last dose of treatment plus 30 days | Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Best Overall Tumor Response (Response Rate) | Baseline until disease progression, new therapy initiated, or death from any cause, up to 12 months after enrollment. | Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=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. Best Overall Tumor Response is complete response plus partial response. |
| Overall Survival | Randomization (≤4 weeks from baseline visit) to 12 months after randomization | Overall survival is the duration from randomization to death. For patients who are alive, overall survival is censored at the date of last contact. |
| Progression-free Survival (PFS) | Randomization (≤4 weeks from baseline visit) to 12 months after randomization | Defined as the time from date of first dose to the first observation of disease progression, or death due to any cause. For patients who are alive and have not progressed, PFS is censored at the date of last radiological assessment. |
Countries
Australia, Italy, Mexico, Spain
Participant flow
Pre-assignment details
Completed is defined as:The patient has completed follow-up visits until 12 months after the randomization date. Qualified Intent-to-Treat (Q-ITT) is defined as: Include all randomized patients, with nonsquamous histology, who comply with their pretreatment folic acid and steroid supplementation schedule and take at least one dose of pemetrexed.
Participants by arm
| Arm | Count |
|---|---|
| Standard Vitamin and Steroid Schedule + Pemetrexed Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment. | 54 |
| Simplified Vitamin and Steroid Schedule + Pemetrexed Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only. | 57 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death from Adverse Event | 2 | 2 |
| Overall Study | Death from Study Disease | 32 | 32 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Standard Vitamin and Steroid Schedule + Pemetrexed | Simplified Vitamin and Steroid Schedule + Pemetrexed | Total |
|---|---|---|---|
| Age Continuous | 62.1 years STANDARD_DEVIATION 11.08 | 60.9 years STANDARD_DEVIATION 12.13 | 61.4 years STANDARD_DEVIATION 11.6 |
| Body Mass Index (BMI) | 25.3 kg/m^2 STANDARD_DEVIATION 3.98 | 26.0 kg/m^2 STANDARD_DEVIATION 5.2 | 25.7 kg/m^2 STANDARD_DEVIATION 4.64 |
| Disease Stage IIIA | 3 Participants | 1 Participants | 4 Participants |
| Disease Stage IIIB | 9 Participants | 13 Participants | 22 Participants |
| Disease Stage IV | 42 Participants | 43 Participants | 85 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0- Fully Active | 26 participants | 26 participants | 52 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1- Ambulatory, Restricted Strenuous Activity | 28 participants | 28 participants | 56 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2- Ambulatory, No Work Activities | 0 participants | 2 participants | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Not Assessed | 0 participants | 1 participants | 1 participants |
| Pathological Diagnosis Cytological | 17 Participants | 21 Participants | 38 Participants |
| Pathological Diagnosis Histopathological | 37 Participants | 36 Participants | 73 Participants |
| Region of Enrollment Australia | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Italy | 15 participants | 18 participants | 33 participants |
| Region of Enrollment Mexico | 27 participants | 27 participants | 54 participants |
| Region of Enrollment Spain | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 22 Participants | 18 Participants | 40 Participants |
| Sex: Female, Male Male | 32 Participants | 39 Participants | 71 Participants |
| Smoking Status Current Smoker | 8 Participants | 9 Participants | 17 Participants |
| Smoking Status Never Smoked | 14 Participants | 15 Participants | 29 Participants |
| Smoking Status Past Smoker | 32 Participants | 33 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 47 / 54 | 54 / 57 |
| serious Total, serious adverse events | 18 / 54 | 18 / 57 |
Outcome results
Primary
Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity
Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section.
Time frame: From first dose of treatment to last dose of treatment plus 30 days
Population: Qualified Intention to Treat (Q-ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Vitamin and Steroid Schedule + Pemetrexed | Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity | 15 participants |
| Simplified Vitamin and Steroid Schedule + Pemetrexed | Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity | 18 participants |
95% CI: [-0.1, 0.28]Linear probability model
Secondary
Overall Survival
Overall survival is the duration from randomization to death. For patients who are alive, overall survival is censored at the date of last contact.
Time frame: Randomization (≤4 weeks from baseline visit) to 12 months after randomization
Population: Qualified Intent to Treat (Q-ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin and Steroid Schedule + Pemetrexed | Overall Survival | 8.2 months |
| Simplified Vitamin and Steroid Schedule + Pemetrexed | Overall Survival | 9.2 months |
p-value: 0.6791Log Rank
95% CI: [0.54, 1.49]Regression, Cox
Secondary
Progression-free Survival (PFS)
Defined as the time from date of first dose to the first observation of disease progression, or death due to any cause. For patients who are alive and have not progressed, PFS is censored at the date of last radiological assessment.
Time frame: Randomization (≤4 weeks from baseline visit) to 12 months after randomization
Population: Qualified Intent to Treat (Q-ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin and Steroid Schedule + Pemetrexed | Progression-free Survival (PFS) | 3.7 months |
| Simplified Vitamin and Steroid Schedule + Pemetrexed | Progression-free Survival (PFS) | 3.8 months |
p-value: 0.587Log Rank
95% CI: [0.57, 1.38]Regression, Cox
Secondary
Proportion of Participants With Best Overall Tumor Response (Response Rate)
Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=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. Best Overall Tumor Response is complete response plus partial response.
Time frame: Baseline until disease progression, new therapy initiated, or death from any cause, up to 12 months after enrollment.
Population: Qualified Intent to Treat (Q-ITT)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard Vitamin and Steroid Schedule + Pemetrexed | Proportion of Participants With Best Overall Tumor Response (Response Rate) | 0.118 proportion of patients |
| Simplified Vitamin and Steroid Schedule + Pemetrexed | Proportion of Participants With Best Overall Tumor Response (Response Rate) | 0.064 proportion of patients |
p-value: 0.4902Fisher Exact