Non-Small-Cell Lung Cancer
Conditions
Brief summary
This study will estimate the response rate in patients with advanced or metastatic non-squamous Non-Small Cell Lung Cancer. Patients who don't progress after 4 to 6 cycles of induction treatment with pemetrexed, cisplatin and cetuximab will receive maintenance treatment with pemetrexed and cetuximab.
Interventions
DRUGPemetrexed
Induction therapy: 500 mg/m², intravenous, on Day 1 of each 21-day cycle for 4 to 6 cycles Maintenance therapy: 500 mg/m², intravenous, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation
DRUGCisplatin
Induction therapy: 75 mg/m², intravenous, on Day 1 of each 21-day cycle for 4 to 6 cycles
DRUGCetuximab
Induction therapy: Loading dose of 400 mg/m², intravenous, on Day 1 of cycle 1, then 250 mg/m², intravenous, weekly for 4 to 6 cycles, 21 day cycles Maintenance therapy: 250 mg/m², intravenous, weekly until progressive disease or treatment discontinuation
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
* Patient must sign an informed consent document for clinical and translational research. * Patient must have locally advanced or metastatic nonsquamous Non-Small Cell Lung Cancer. * Patient must have biological tissue available from your diagnosis tumor for detection of some biomarkers (translational research). * Patient cannot be receiving nor have received any prior systemic anticancer therapy, immunotherapy, targeted therapy, or biological therapy for your lung cancer (except chemotherapy given after surgery if it has been completed more than one year before the study entry). * Patient is allowed to have had prior radiation therapy as long as it was not more than 25% of the bone marrow and did not include the whole pelvis. Prior radiation therapy should be completed at least 2 weeks prior to first study drug. Thoracic radiation must be completed more than 12 weeks before the study entry. You must be recovered from the toxic effects. * Patient must have at least 1 measurable tumor lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. * Patient must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work. * Test results assessing the function of blood forming tissue, kidneys, and liver must be satisfactory. * Females must be sterile, postmenopausal or on contraception. * Males must be on contraception or sterile (for example post-vasectomy).
Exclusion criteria
* Patient cannot have symptomatic central nervous system metastases. * Patient cannot have an active infection or other serious condition that your doctor thinks would make you unable to participate. * Patient cannot have a serious cardiac condition, such as a heart attack, angina, or heart disease within 6 months of entering the trial. * Patient cannot have had a another form of cancer other than superficial basal cell and superficial squamous (skin) cell cancer, or carcinoma in situ of the cervix within the last 5 years. * Patient cannot have had significant neurologic or psychiatric disorders including dementia, seizures and bipolar disorder. * Patient cannot have moderate or severe peripheral neuropathy * Patient cannot have received treatment within 30 days with any experimental drug. * Patient cannot have had a major surgery within the last 4 weeks. * Patient cannot have previously received treatment with transduction inhibitors or Epidermal Growth Factor Receptor (EGFR)-targeting therapy. * Patient cannot have prior known allergic/hypersensitivity reaction to any of the components of study treatments. * Females cannot be pregnant or breastfeeding. * Patient is unable to stop taking more than 1.3 grams of aspirin on a daily basis or other aspirin like medication (non-steroidal antiinflammatory drugs: NSAIDs) for a few days during each cycle of therapy. * Patient is unable or unwilling to take folic acid, injections of vitamin B12, or corticosteroids. * Patient cannot have fluid around your lungs or in your abdomen (pleural effusions or ascites) that cannot be controlled by drainage or other procedures. * Patient cannot have received a yellow fever vaccination within the previous 30 days or plan to have it. * Patient cannot have known drug abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Tumor Response (Objective Tumor Response Rate) | From start of treatment until documented best response. (up to 18.9 months) | Response was assessed 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. Tumor response is presented as a percentage (%) and is the number of participants with a CR plus PR divided by the number of participants in the protocol qualified (PQ) population, then multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From start of treatment until documented disease progression or death from any cause (up to 18.9 months) | PFS is measured from study entry until disease progression, death or date of last contact. Progressive disease (PD) was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants not known to have died or have had objective PD as of the data cutoff date, PFS was censored at the date of the last objective progression-free disease assessment. |
| The Percentage of Participants Still Living at One Year (One Year Survival Rate) | One year | The one year survival rate is presented as percentage (%) of participants still living at one year and is the number of participants that are still alive at one year divided by the number of participants in the protocol qualified (PQ) population, which is then multiplied by 100. |
| The Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | From start of treatment until documented best tumor response (up to 18.9 months) | The DCR is presented as percentage (%) and is the number of participants with a best tumor response of CR, PR, or SD divided by the number of participants in the protocol qualified (PQ) population, then multiplied by 100. Best tumor response of CR, PR, or SD was determined from the sequence of tumor response assessments. Tumor response was assessed using RECIST criteria. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; SD=small changes that do not meet above criteria. |
Countries
Austria, Germany, Greece, Italy, Netherlands, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pem/Cis + Cet Induction Therapy: 500 mg/m² pemetrexed (Pem)on Day 1 of every 21-day cycle, 75 mg/m² cisplatin (Cis) on Day 1 of every 21-day cycle and 400 mg/m² cetuximab (Cet) given intravenously (IV) on Day 1 of Cycle 1 and 250 mg/m² once weekly thereafter. Induction period is 4 to 6 cycles.
Maintenance Therapy: 500 mg/m² pemetrexed (Pem) given intravenously (IV) on Day 1 of each 21 day cycle and 250 mg/m² cetuximab (Cet) given weekly until progressive disease (PD) or treatment discontinuation. | 113 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Period | Death due to serious adverse event | 6 |
| Induction Period | Death due to Study Disease | 4 |
| Induction Period | Nonserious Adverse Event | 5 |
| Induction Period | Physician Decision | 3 |
| Induction Period | Progressive Disease (PD) | 25 |
| Induction Period | Protocol Violation | 1 |
| Induction Period | Serious Adverse Event | 10 |
| Induction Period | Withdrawal by Subject | 8 |
| Maintenance Period | On-going in the Study at Data Cut-off | 4 |
Baseline characteristics
| Characteristic | Pem/Cis + Cet |
|---|---|
| Age, Continuous | 59.15 years STANDARD_DEVIATION 8.83 |
| Disease Stage Stage IIIB | 9 participants |
| Disease Stage Stage IV | 104 participants |
| Eastern Co-operative Oncology Group (ECOG) Performance Status 0 - Fully Active | 56 participants |
| Eastern Co-operative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 57 participants |
| Pathological Diagnosis Adenocarcinoma (Adeno), Breast | 1 participants |
| Pathological Diagnosis Carcinoma, Adenosquamous,Lung, Predominantly Adeno | 1 participants |
| Pathological Diagnosis Large Cells Lung Carcinoma | 5 participants |
| Pathological Diagnosis Malignant Neoplasm, Adeno Lung | 88 participants |
| Pathological Diagnosis Missing | 1 participants |
| Pathological Diagnosis Non-Small Cell Lung (NSCL) Cancer | 9 participants |
| Pathological Diagnosis Poorly Differentiated Non-Small Cell | 8 participants |
| Race/Ethnicity, Customized White | 113 participants |
| Region of Enrollment Austria | 6 participants |
| Region of Enrollment Germany | 28 participants |
| Region of Enrollment Greece | 12 participants |
| Region of Enrollment Italy | 26 participants |
| Region of Enrollment Netherlands | 16 participants |
| Region of Enrollment Spain | 25 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 101 / 113 |
| serious Total, serious adverse events | 61 / 113 |
Outcome results
Primary
Percentage of Participants With a Tumor Response (Objective Tumor Response Rate)
Response was assessed 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. Tumor response is presented as a percentage (%) and is the number of participants with a CR plus PR divided by the number of participants in the protocol qualified (PQ) population, then multiplied by 100.
Time frame: From start of treatment until documented best response. (up to 18.9 months)
Population: Outcome measure was assessed using the Protocol Qualified (PQ) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pem/Cis + Cet | Percentage of Participants With a Tumor Response (Objective Tumor Response Rate) | 38.5 percentage of participants |
80% CI: [32.3, 45.09]
Secondary
Progression-free Survival (PFS)
PFS is measured from study entry until disease progression, death or date of last contact. Progressive disease (PD) was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants not known to have died or have had objective PD as of the data cutoff date, PFS was censored at the date of the last objective progression-free disease assessment.
Time frame: From start of treatment until documented disease progression or death from any cause (up to 18.9 months)
Population: Outcome measure was assessed using the Protocol Qualified (PQ) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pem/Cis + Cet | Progression-free Survival (PFS) | 5.82 months |
80% CI: [4.4, 6.7]
Secondary
The Percentage of Participants Still Living at One Year (One Year Survival Rate)
The one year survival rate is presented as percentage (%) of participants still living at one year and is the number of participants that are still alive at one year divided by the number of participants in the protocol qualified (PQ) population, which is then multiplied by 100.
Time frame: One year
Population: Outcome measure was assessed using the Protocol Qualified (PQ) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pem/Cis + Cet | The Percentage of Participants Still Living at One Year (One Year Survival Rate) | 45 percentage of participants |
80% CI: [39, 51]
Secondary
The Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])
The DCR is presented as percentage (%) and is the number of participants with a best tumor response of CR, PR, or SD divided by the number of participants in the protocol qualified (PQ) population, then multiplied by 100. Best tumor response of CR, PR, or SD was determined from the sequence of tumor response assessments. Tumor response was assessed using RECIST criteria. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; SD=small changes that do not meet above criteria.
Time frame: From start of treatment until documented best tumor response (up to 18.9 months)
Population: Outcome measure was assessed using the Protocol Qualified (PQ) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pem/Cis + Cet | The Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | 59.6 percentage of participants |
80% CI: [53.06, 65.94]