Carcinoma, Non-Small Cell Lung Cancer
Conditions
Brief summary
The main purpose of this study of pemetrexed combined with cisplatin used as neoadjuvant chemotherapy (2 or 3 cycles) in participants with operable non-small cell lung cancer (NSCLC) is to look at various genes present in participants' blood and tumor tissue to see if there is any link between the levels or changes in the genes and how participants with lung cancer respond to pemetrexed and cisplatin treatment.
Interventions
DRUGpemetrexed
500 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs
DRUGcisplatin
75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs
PROCEDURERadical Non-Small Cell Lung Cancer (NSCLC) surgery
All participants proceeded to surgery within 4-8 weeks from the last dose of pemetrexed.
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
* pathologic documentation of non-small cell lung cancer (NSCLC) * tumor must be accessible by bronchoscopy for tumor tissue sample collection * patients must have lung cancer with clinical stage IB, II, IIIA * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * patients must not have received prior systemic chemotherapy or radiation therapy for NSCLC (prior resection of lung is allowed provided at least 5 years have elapsed between prior surgery and enrolment)
Exclusion criteria
* bronchoalveolar carcinoma or stage IIIA tumor involving the superior sulcus (Pancoast tumors) * pregnant or breast feeding patients * patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry * patients with history or presence of other malignancy except in situ carcinoma of the skin or prior malignancy treated more than 5 years before without recurrence (excluding melanoma, breast cancer and hypernephroma) * unwillingness to take folic acid or vitamin B12 supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood | Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed) | Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Tumor Response (Response Rate) | Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed) | Tumor response to treatment using 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 (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Response rate was estimated as the total number of CR or PR, divided by the total number of participants treated. |
| Duration of Response | Time of response to disease progression (up to 44.4 months) | The duration of response was defined as the time from complete response (CR) or partial response (PR) to disease progression. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions. |
| Disease Free Survival (DFS) | Treatment start to disease progression or death from any cause (up to 45.5 months) | DFS was the time from date of first dose to first observation of progressive disease (PD) or death due to any cause. PD=20% increase in sum of longest diameter of target lesions. If a participant was not known to have died or have PD, DFS was censored at the date of the last objective progression-free disease assessment. |
| Overall Survival (OS) | Treatment start to death from any cause (up to 47.6 months) | OS was defined as the time from treatment start to death from any cause. For participants who were alive, OS was censored at the last contact date. |
Countries
Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Cisplatin Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs.
Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Pemetrexed + Cisplatin |
|---|---|
| Age Continuous | 55.94 years STANDARD_DEVIATION 8.214 |
| Basis for Diagnosis Cytological | 0 participants |
| Basis for Diagnosis Histopathological | 30 participants |
| Initial Pathological Diagnosis Adenocarcinoma of Lung | 2 participants |
| Initial Pathological Diagnosis Bronchoalveolar Carcinoma | 0 participants |
| Initial Pathological Diagnosis Large Cell Carcinoma of Lung | 0 participants |
| Initial Pathological Diagnosis Mixed Cell Carcinoma of Lung | 0 participants |
| Initial Pathological Diagnosis Other | 8 participants |
| Initial Pathological Diagnosis Squamous Cell Carcinoma of Lung | 20 participants |
| Race/Ethnicity, Customized Caucasian | 30 participants |
| Region of Enrollment Poland | 30 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 29 Participants |
| Stage of Disease at Study Entry Stage IB | 18 participants |
| Stage of Disease at Study Entry Stage IIA | 2 participants |
| Stage of Disease at Study Entry Stage IIB | 10 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 30 |
| serious Total, serious adverse events | 4 / 30 |
Outcome results
Primary
High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood
Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done.
Time frame: Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed)
Population: Due to lack of eligible participants, enrollment was stopped early when 30 participants were enrolled. Tumor samples were collected in only 19 of these 30 participants. Results obtained from analyses of a small number of available samples were considered to be of little scientific and medical relevance, and tumor-tissue analyses were not conducted.
Secondary
Disease Free Survival (DFS)
DFS was the time from date of first dose to first observation of progressive disease (PD) or death due to any cause. PD=20% increase in sum of longest diameter of target lesions. If a participant was not known to have died or have PD, DFS was censored at the date of the last objective progression-free disease assessment.
Time frame: Treatment start to disease progression or death from any cause (up to 45.5 months)
Population: DFS was evaluated on all qualified enrolled patients who received at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Disease Free Survival (DFS) | 43.7 months |
Secondary
Duration of Response
The duration of response was defined as the time from complete response (CR) or partial response (PR) to disease progression. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions.
Time frame: Time of response to disease progression (up to 44.4 months)
Population: Duration of response was analyzed on responders treated with at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy; responder.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Duration of Response | 42.5 months |
Secondary
Overall Survival (OS)
OS was defined as the time from treatment start to death from any cause. For participants who were alive, OS was censored at the last contact date.
Time frame: Treatment start to death from any cause (up to 47.6 months)
Population: OS was evaluated on all qualified enrolled patients who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Cisplatin | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants With Objective Tumor Response (Response Rate)
Tumor response to treatment using 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 (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Response rate was estimated as the total number of CR or PR, divided by the total number of participants treated.
Time frame: Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed)
Population: Tumor response rate and 95% confidence interval (CI) of best CR or PR were evaluated on all qualified enrolled participants treated with at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Cisplatin | Percentage of Participants With Objective Tumor Response (Response Rate) | 34.5 percentage of participants |