Non-Small Cell Lung Cancer
Conditions
Brief summary
This study is a multicenter, open-label, two-arm, randomized, parallel Phase 2 feasibility study of pemetrexed in combination with either cisplatin (Arm A) or carboplatin (Arm B) as adjuvant combination-chemotherapy in participants with completely resected, stage Ib or IIa/IIb non-small cell lung cancer (NSCLC). A two-stage design will be employed independently for both treatment arms, with the possibility of stopping each treatment early for lack of feasibility.
Interventions
DRUGpemetrexed
500 milligrams per square meter (mg/m\^2), intravenous (IV), every 21 days x 4 cycles
DRUGcisplatin
75 mg/m\^2, intravenous (IV), every 21 days x 4 cycles
DRUGcarboplatin
area under the curve (AUC) 5 milligrams per milliliter\*minute (mg/ml\*min), intravenous (IV), every 21 days x 4 cycles
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
* Histologically proven non-small cell lung cancer stage Ib, IIa or IIb * Must have complete tumor resection by pneumonectomy or lobectomy * Must have been surgically proven to be N2 negative
Exclusion criteria
* Serious concomitant systemic disorder * Post-operative complications or other surgery related conditions * A prior malignancy other than NSCLC unless that malignancy was diagnosed and treated at least 5 years ago
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Feasibility of Post-Surgery Chemotherapy | every 21-day cycle for 4 cycles up to 30 days after last infusion | Feasibility was measured by completion of 4 treatment cycles without remaining toxicities \>=Grade 3 at 30 days after last infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade III/IV Adverse Events | every 21-day cycle for 4 cycles | Number of participants experiencing Grade III/IV hematologic and non-hematologic adverse events possibly related to study drug or protocol procedures in this study. |
| Overall Survival at 3 Years | baseline to date of death from any cause, assessed at 3 years | For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year survival rate. Results are presented as probability (%) of survival at 3 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date. |
| 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years | length of time disease free, assessed at 3 years | For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year disease-free rate. Disease-free survival is defined as the time from enrollment to the first observation of disease progression, or death due to any cause. For participants not known to have died and to have had recurrent disease, disease-free survival was censored at the date of the last participant contact with No Recurrence status. Results are presented as probability (%) of disease-free survival at 3 years. |
| Overall Survival at 6 Years | Baseline to date of death from any cause assessed at 6 years | For each treatment arm, the Kaplan-Meier technique was used to estimate the 6 year survival rate. Results are presented as probability (%) of survival at 6 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date. |
Countries
France, Germany, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Cisplatin Pemetrexed: 500 mg/m\^2, intravenous (IV), every 21 days x 4 cycles Cisplatin: 75 mg/m\^2, intravenous (IV), every 21 days x 4 cycles | 63 |
| Pemetrexed + Carboplatin Pemetrexed: 500 mg/m\^2, intravenous (IV), every 21 days x 4 cycles Carboplatin: area under the curve (AUC) 5 mg/ml\*min, intravenous (IV), every 21 days x 4 cycles | 59 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Pemetrexed + Cisplatin | Pemetrexed + Carboplatin | Total |
|---|---|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 7.7 | 58.9 years STANDARD_DEVIATION 7.2 | 59.7 years STANDARD_DEVIATION 7.5 |
| Curative Surgery Used Bi-lobectomy | 8 participants | 4 participants | 12 participants |
| Curative Surgery Used Lobectomy | 46 participants | 46 participants | 92 participants |
| Curative Surgery Used Pneumonectomy | 9 participants | 9 participants | 18 participants |
| Race/Ethnicity, Customized African | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 62 participants | 58 participants | 120 participants |
| Region of Enrollment France | 12 participants | 8 participants | 20 participants |
| Region of Enrollment Germany | 44 participants | 43 participants | 87 participants |
| Region of Enrollment Spain | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 14 Participants | 18 Participants | 32 Participants |
| Sex: Female, Male Male | 49 Participants | 41 Participants | 90 Participants |
| Smoking History No | 7 participants | 3 participants | 10 participants |
| Smoking History Yes | 56 participants | 56 participants | 112 participants |
| Stage of Disease Prior to Tumor Resection Stage Ia | 0 participants | 1 participants | 1 participants |
| Stage of Disease Prior to Tumor Resection Stage Ib | 27 participants | 26 participants | 53 participants |
| Stage of Disease Prior to Tumor Resection Stage IIa | 6 participants | 5 participants | 11 participants |
| Stage of Disease Prior to Tumor Resection Stage IIb | 30 participants | 25 participants | 55 participants |
| Stage of Disease Prior to Tumor Resection Stage IIIa | 0 participants | 1 participants | 1 participants |
| Stage of Disease Prior to Tumor Resection Unknown: could have been either Stage IIIb or IV | 0 participants | 1 participants | 1 participants |
| Tumor Type at Initial Pathological Diagnosis Adenocarcinoma of the Lung | 27 participants | 23 participants | 50 participants |
| Tumor Type at Initial Pathological Diagnosis Bronchoalveolar Carcinoma | 2 participants | 0 participants | 2 participants |
| Tumor Type at Initial Pathological Diagnosis Large Cell Carcinoma of Lung | 5 participants | 7 participants | 12 participants |
| Tumor Type at Initial Pathological Diagnosis Mixed Cell (Squamous/Adeno) Carcinoma of Lung | 0 participants | 5 participants | 5 participants |
| Tumor Type at Initial Pathological Diagnosis Non-Small Cell Lung Cancer | 5 participants | 4 participants | 9 participants |
| Tumor Type at Initial Pathological Diagnosis Squamous Carcinoma of the Lung | 24 participants | 20 participants | 44 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 64 | 52 / 54 |
| serious Total, serious adverse events | 18 / 64 | 5 / 54 |
Outcome results
Primary
The Feasibility of Post-Surgery Chemotherapy
Feasibility was measured by completion of 4 treatment cycles without remaining toxicities \>=Grade 3 at 30 days after last infusion.
Time frame: every 21-day cycle for 4 cycles up to 30 days after last infusion
Population: Number of participants in safety population, that is, number of participants enrolled, randomized and treated with at least one dose of study drug (presented by treatment received arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Cisplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Early Discontinuation | 18 participants |
| Pemetrexed + Cisplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Remaining Grade 3/4 Toxicity | 4 participants |
| Pemetrexed + Cisplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Lost to Follow-up | 1 participants |
| Pemetrexed + Cisplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Underdosage (<95% intended dose) | 5 participants |
| Pemetrexed + Cisplatin | The Feasibility of Post-Surgery Chemotherapy | Participants feasible | 38 participants |
| Pemetrexed + Carboplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Underdosage (<95% intended dose) | 19 participants |
| Pemetrexed + Carboplatin | The Feasibility of Post-Surgery Chemotherapy | Participants feasible | 27 participants |
| Pemetrexed + Carboplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Early Discontinuation | 6 participants |
| Pemetrexed + Carboplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Lost to Follow-up | 2 participants |
| Pemetrexed + Carboplatin | The Feasibility of Post-Surgery Chemotherapy | Non-feasible = Remaining Grade 3/4 Toxicity | 3 participants |
95% CI: [46.4, 71.5]
95% CI: [36.1, 63.9]
Secondary
3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years
For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year disease-free rate. Disease-free survival is defined as the time from enrollment to the first observation of disease progression, or death due to any cause. For participants not known to have died and to have had recurrent disease, disease-free survival was censored at the date of the last participant contact with No Recurrence status. Results are presented as probability (%) of disease-free survival at 3 years.
Time frame: length of time disease free, assessed at 3 years
Population: All randomized participants. Intent to Treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Cisplatin | 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years | 61.2 probability of disease-free survival (%) |
| Pemetrexed + Carboplatin | 3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years | 67.3 probability of disease-free survival (%) |
Secondary
Grade III/IV Adverse Events
Number of participants experiencing Grade III/IV hematologic and non-hematologic adverse events possibly related to study drug or protocol procedures in this study.
Time frame: every 21-day cycle for 4 cycles
Population: Number of participants in safety population, that is, number of participants enrolled, randomized and treated with at least one dose of study drug (presented by treatment received arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Hyperglycaemia | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Vomiting | 3 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Fatigue | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Neutropenia | 9 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Anaemia | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Thrombocytopenia | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Febrile neutropenia | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Leukopenia | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Lymphopenia | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Neutrophil count decreased | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Haemoglobin count decreased | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Platelet count decreased | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | White blood cell count decreased | 0 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Asthenia | 4 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Nausea | 3 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Catheter related infection | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Gamma-glutamyltransferase increased | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Anorexia | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Hyperkalaemia | 1 participants |
| Pemetrexed + Cisplatin | Grade III/IV Adverse Events | Psychotic disorder | 1 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Psychotic disorder | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Platelet count decreased | 1 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Vomiting | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Gamma-glutamyltransferase increased | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | White blood cell count decreased | 2 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Neutropenia | 6 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Hyperkalaemia | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Anaemia | 3 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Asthenia | 2 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Thrombocytopenia | 3 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Anorexia | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Febrile neutropenia | 2 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Nausea | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Leukopenia | 1 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Fatigue | 2 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Lymphopenia | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Hyperglycaemia | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Neutrophil count decreased | 6 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Catheter related infection | 0 participants |
| Pemetrexed + Carboplatin | Grade III/IV Adverse Events | Haemoglobin count decreased | 2 participants |
Secondary
Overall Survival at 3 Years
For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year survival rate. Results are presented as probability (%) of survival at 3 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date.
Time frame: baseline to date of death from any cause, assessed at 3 years
Population: All randomized participants. Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Cisplatin | Overall Survival at 3 Years | 82.0 percent probability of survival (%) |
| Pemetrexed + Carboplatin | Overall Survival at 3 Years | 83.2 percent probability of survival (%) |
Secondary
Overall Survival at 6 Years
For each treatment arm, the Kaplan-Meier technique was used to estimate the 6 year survival rate. Results are presented as probability (%) of survival at 6 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date.
Time frame: Baseline to date of death from any cause assessed at 6 years
Population: All randomized participants. Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Cisplatin | Overall Survival at 6 Years | 72.6 percent probability of survival (%) |
| Pemetrexed + Carboplatin | Overall Survival at 6 Years | 83.2 percent probability of survival (%) |