Lung Cancer
Conditions
Keywords
stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer
Brief summary
RATIONALE: Diagnostic procedures, such as positron emission tomography (PET), (done before, during, and after chemotherapy) may help doctors predict a patient's response to treatment and help plan the best treatment. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well PET works in predicting response in patients who are undergoing treatment with pemetrexed disodium and cisplatin with or without surgery for stage I, stage II, or stage III non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Determine the effectiveness of fludeoxyglucose F 18 positron emission tomography in predicting radiological and pathological response in patients treated with pemetrexed disodium and cisplatin with or without surgery for stage IB-IIIB non-small cell lung cancer (NSCLC). Secondary * Determine the safety of cisplatin and pemetrexed disodium in these patients. * Determine the radiographic response rate, duration of response, and time to progression in patients treated with cisplatin and pemetrexed disodium. OUTLINE: This is a multicenter study. * Fludeoxyglucose F 18 (18FDG) positron emission tomography (PET) imaging: All patients undergo positron emission tomography (PET) imaging of the head, neck, thorax, abdomen, and pelvis. Patients receive fludeoxyglucose F 18 (\^18FDG) IV followed by 45 minutes of rest. PET imaging is done over 1 hour and 8 minutes. Patients undergo PET imaging at three points during the study: 4 weeks prior to treatment, after the first cycle of treatment, and after 3 courses of chemotherapy. Some patients then undergo surgical resection of the tumor. * Chemotherapy: Patients receive cisplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Interventions
DRUGcisplatin
DRUGpemetrexed disodium
PROCEDUREadjuvant therapy
PROCEDUREtherapeutic conventional surgery
RADIATIONfludeoxyglucose F 18
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Stage IB, II, IIIA, or IIIB (T4, N0-1) disease * Staging must have been performed 4 weeks prior to study entry with a CT scan of chest, upper abdomen, and fludeoxyglucose F 18 (\^18FDG) positron emission tomography (PET) scan * Mediastinal evaluation and staging based on combination of CT scan and FDG-PET results * If N1 or N2 nodes are found by FDG-PET or CT scan, metastases must be ruled out by brain MRI * Measurable and resectable disease * T4 lesions must be resectable * Eligible for curative surgery * No malignant pleural effusion PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,250/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 3.0 times ULN Renal * Creatinine clearance ≥ 45 mL/min Pulmonary * Adequate pulmonary reserve to undergo surgery * Predicted FEV\_1 \> 0.8 L after resection Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * Able to take corticosteroids * Able to take folic acid or vitamin B\_12 supplements * No other malignancy within the past 5 years except nonmelanoma skin cancer or noninvasive cervical cancer * No concurrent serious or uncontrolled disorder that would preclude study participation * No type I diabetes mellitus * Type II diabetes mellitus allowed if glucose is 80-150 mg/dL PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy * No concurrent prophylactic filgrastim (G-CSF) * No concurrent thrombopoiesis-stimulating agents Chemotherapy * At least 5 years since prior chemotherapy Endocrine therapy * No concurrent anticancer hormonal therapy Radiotherapy * No prior radiotherapy to the chest * No concurrent curative or palliative radiotherapy Surgery * Not specified Other * At least 30 days since prior non-FDA-approved or investigational agents * At least 5 days since prior aspirin or other nonsteroidal anti-inflammatory agents (8 days for long-acting agents \[e.g., piroxicam\]) * No other concurrent anticancer therapy * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positron Emission Tomography as a Predictor of Response Measured by the Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy | Between days 18 and 22 prior to second chemotherapy infusion | Number of Participants with Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Neoadjuvant Chemotherapy | Up to 4 weeks after last dose of chemotherapy | The number of patients that experienced a grade 3 or higher adverse event. |
| Efficacy of Neoadjuvant Chemotherapy as Measured by Radiologic Response Rate | Up to 4 weeks after last dose of chemotherapy | The number of patients that had either a CR, PR or SD after the completion of chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant Therapy, PET Scan and Surgery cisplatin
pemetrexed disodium
adjuvant therapy
therapeutic conventional surgery
fludeoxyglucose F 18 | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Neoadjuvant Therapy, PET Scan and Surgery |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 62 years |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 25 |
| serious Total, serious adverse events | 1 / 25 |
Outcome results
Primary
Positron Emission Tomography as a Predictor of Response Measured by the Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy
Number of Participants with Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy
Time frame: Between days 18 and 22 prior to second chemotherapy infusion
Population: Only 19 patients had PET scans at both baseline and day 18-22 available for review.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Therapy, PET Scan and Surgery | Positron Emission Tomography as a Predictor of Response Measured by the Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy | 11 Participants |
Secondary
Efficacy of Neoadjuvant Chemotherapy as Measured by Radiologic Response Rate
The number of patients that had either a CR, PR or SD after the completion of chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: Up to 4 weeks after last dose of chemotherapy
Population: One patient was excluded from the efficacy analysis because they were subsequently found to be ineligible. Three patients were unevaluable because they did not have have a CT scan after the completion of chemotherapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Therapy, PET Scan and Surgery | Efficacy of Neoadjuvant Chemotherapy as Measured by Radiologic Response Rate | 20 Participants |
Secondary
Safety of Neoadjuvant Chemotherapy
The number of patients that experienced a grade 3 or higher adverse event.
Time frame: Up to 4 weeks after last dose of chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Therapy, PET Scan and Surgery | Safety of Neoadjuvant Chemotherapy | 10 Participants |