Non-Small Cell Lung Cancer
Conditions
Brief summary
Thymidylate synthase (TS) is a substance the body produces naturally. The purpose of this research is to determine if there is a link between TS production and how well patients respond to treatment of non-squamous non-small cell lung cancer (NSCLC). The aim for the future is that doctors could have a better understanding in advance about which patients might respond well to pemetrexed based on how much TS they produce.
Detailed description
All patients on this study will receive 4 intravenous injections of the chemotherapy drugs pemetrexed and cisplatin (with each injection approximately 3 weeks apart). Patients who complete 4 such injections and respond well to their treatment may continue to receive an injection of chemotherapy drug pemetrexed (approximately every 3 weeks). In general terms, treatment will last until either the patient or the doctor decides that there is no clear benefit in continuing with the treatment. TS levels will be measured from the tumour sample used to make the original diagnosis of NSCLC.
Interventions
DRUGpemetrexed
Induction Therapy: 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
DRUGcisplatin
Induction Therapy: 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have Stage 3B or 4 Non-Small Cell Lung Cancer of the non- squamous type * Patients must at least be able to be physically mobile, take care of yourself and be able to perform light activities such as light housework or office work * Patients must not have had previous chemotherapy treatment for lung cancer * Patients must not have had radiotherapy in the last 30 days * Patients must have measureable tumor lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated on computed tomography (CT) scan * Patients' test results assessing the function of their blood forming tissue, kidneys, liver and lungs are satisfactory * Women must be sterile, postmenopausal or on contraception and men must be sterile or on contraception
Exclusion criteria
* Patients cannot have received other investigational drugs within the last 30 days * Patients cannot have any serious, uncontrolled medical condition that might compromise their ability to take part in the study safely * Patients cannot have a current second primary malignant tumor * Patients cannot be having current treatment with any other anti-tumor therapy * Patients cannot have had a yellow fever vaccination within 30 days of enrolment * Patients who are unable to take vitamins (including injections of vitamin B12) or oral cortisone medication * Patients who are unable to stop taking more than 1.3 grams of aspirin on a daily basis or non-steroidal anti-inflammatory agents * Patients who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline to measured progressive disease with follow-up every 6 weeks until progression of disease (up to 18 months after the last participant commenced induction therapy) | PFS is time from first dose to first observation of disease progression/death (any cause). PFS is reported for participants with thymidylate synthase (TS) scores. For participants not known to have died by the data cut-off date and who do not have progressive disease, PFS will be censored at date of last objective progression-free disease assessment. For participants who receive systemic anticancer therapy after study drug discontinuation and prior to disease progression/death, PFS will be censored at date of last objective progression-free disease assessment prior to chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tumor Response (Tumor Response Rate) | Baseline to disease progression (up to 20 months) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response=disappearance of all target lesions; Partial Response=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. Percentage of participants with tumor response was determined by the number of participants with PR or CR (confirmed or not) divided by the total number of treated participants multiplied by 100. |
| Percentage of Participants With Concordance Between Local and Central Histological Diagnosis | Baseline | A centralized pathology review on all enrolled participants was performed to confirm the histological diagnosis performed at the site. Upon review of the local diagnosis obtained at the respective site, the central reviewer established whether or not there was an agreement between the local and central diagnosis. The percentage of participants with concordance was defined as the number of participants for which there was an agreement divided by the number of treated participants (concordance rate) multiplied by 100. |
| Percentage of Participants Surviving at 18 Months (Overall Survival Rate) | Baseline to date of death (up to 24.5 months) | The percentage of participants surviving at 18 months was defined as the number of treated participants who had not died prior to 18 months from the date of their first dose divided by the total number of treated participants multiplied by 100. For participants who are alive, overall survival was censored at the last contact. |
Countries
Ireland, United Kingdom
Participant flow
Pre-assignment details
The trial consists of induction therapy (up to 4 cycles of pemetrexed-cisplatin treatment) and maintenance therapy (pemetrexed only). Only participants who do not develop disease progression during induction therapy are eligible to receive maintenance therapy.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Therapy | Adverse Event | 8 |
| Induction Therapy | Death due to Study Disease | 4 |
| Induction Therapy | Death due to Study Drug Toxicity | 1 |
| Induction Therapy | Physician Decision | 1 |
| Induction Therapy | Progressive Disease | 13 |
| Maintenance Therapy | Adverse Event | 16 |
| Maintenance Therapy | Death due to adverse event | 1 |
| Maintenance Therapy | Physician Decision | 1 |
| Maintenance Therapy | Progressive Disease | 25 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| Age Continuous | 63.0 years STANDARD_DEVIATION 9.42 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0- Fully active | 24 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1- Ambulatory, Restricted Strenuous Activity | 46 participants |
| Past and Current Tobacco Usage Ever used tobacco products | 64 participants |
| Past and Current Tobacco Usage Never used tobacco products | 6 participants |
| Pathological Diagnosis Adenocarcinoma, acinar | 1 participants |
| Pathological Diagnosis Adenocarcinoma, not otherwise specified (NOS) | 34 participants |
| Pathological Diagnosis Adenocarcinoma, poorly differentiated | 20 participants |
| Pathological Diagnosis Bronchioalveolar Carcinoma | 6 participants |
| Pathological Diagnosis Carcinoma, Non-Small Cell, Lung (NSCL), (NOS) | 3 participants |
| Pathological Diagnosis Carcinoma, NSC, Poorly Differentiated, Lung | 5 participants |
| Pathological Diagnosis Carcinoma, undifferentiated | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Caucasian | 69 participants |
| Region of Enrollment Ireland | 4 participants |
| Region of Enrollment United Kingdom | 66 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 67 / 70 |
| serious Total, serious adverse events | 41 / 70 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is time from first dose to first observation of disease progression/death (any cause). PFS is reported for participants with thymidylate synthase (TS) scores. For participants not known to have died by the data cut-off date and who do not have progressive disease, PFS will be censored at date of last objective progression-free disease assessment. For participants who receive systemic anticancer therapy after study drug discontinuation and prior to disease progression/death, PFS will be censored at date of last objective progression-free disease assessment prior to chemotherapy.
Time frame: Baseline to measured progressive disease with follow-up every 6 weeks until progression of disease (up to 18 months after the last participant commenced induction therapy)
Population: Population for the efficacy assessment includes all treated participants with a valid TS expression assessment. Six participants were censored for PFS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Progression Free Survival (PFS) | 5.5 months |
p-value: <0.000195% CI: [1.008, 1.021]Regression, Cox
Secondary
Percentage of Participants Surviving at 18 Months (Overall Survival Rate)
The percentage of participants surviving at 18 months was defined as the number of treated participants who had not died prior to 18 months from the date of their first dose divided by the total number of treated participants multiplied by 100. For participants who are alive, overall survival was censored at the last contact.
Time frame: Baseline to date of death (up to 24.5 months)
Population: All enrolled participants. Nineteen participants were censored for overall survival.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed | Percentage of Participants Surviving at 18 Months (Overall Survival Rate) | 37.1 percentage of participants |
Secondary
Percentage of Participants With Concordance Between Local and Central Histological Diagnosis
A centralized pathology review on all enrolled participants was performed to confirm the histological diagnosis performed at the site. Upon review of the local diagnosis obtained at the respective site, the central reviewer established whether or not there was an agreement between the local and central diagnosis. The percentage of participants with concordance was defined as the number of participants for which there was an agreement divided by the number of treated participants (concordance rate) multiplied by 100.
Time frame: Baseline
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed | Percentage of Participants With Concordance Between Local and Central Histological Diagnosis | 78.6 percentage of participants |
Secondary
Percentage of Participants With Tumor Response (Tumor Response Rate)
Tumor response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response=disappearance of all target lesions; Partial Response=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. Percentage of participants with tumor response was determined by the number of participants with PR or CR (confirmed or not) divided by the total number of treated participants multiplied by 100.
Time frame: Baseline to disease progression (up to 20 months)
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed | Percentage of Participants With Tumor Response (Tumor Response Rate) | 30 percentage of participants |