Fludeoxyglucose F-18 PET/CT in Predicting Response to Chemotherapy in Patients With Stage IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

Study Overview
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Brief Summary
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This phase II trial studies how well fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) works in predicting response to chemotherapy in patients with stage IIIA non-small cell lung cancer that can be removed by surgery (resectable). Performing diagnostic procedures, such as fludeoxyglucose F-18 PET/CT, after one course of chemotherapy may help doctors predict a patient's response to treatment earlier and help plan the best treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate whether percent change in maximum standardized uptake value (SUVmax) on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes can predict mediastinal downstaging in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy. SECONDARY OBJECTIVES: I. To evaluate the predictive accuracy for mediastinal downstaging of two other FDG-PET/CT-based markers measured on mediastinal lymph nodes: SUVmax at T1 and change of SUVmax from T0 to T1. II. To evaluate the predictive accuracy for mediastinal downstaging of the FDG-PET/CT-based markers measured on the primary tumor, include percent change of peak standardized uptake value (SUVpeak) (based on PET Response Criteria in Solid Tumors [PERCIST] criteria), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) from T0 to T1. III. To evaluate whether percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes can predict overall survival (OS). OUTLINE: Patients undergo fludeoxyglucose F-18 PET/CT at baseline and after course 1 of chemotherapy. Patients undergo 1 of 3 chemotherapy regimens at the discretion of the investigator. CHEMOTHERAPY REGIMEN 1: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, and 8. Patients also receive cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 3: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 5 years.

Official Title
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Role of Early 18F-FDG-PET/CT Scan in Predicting Mediastinal Downstaging With Neoadjuvant Chemotherapy in Resectable Stage III A NSCLC

Conditions
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Stage IIIA Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Procedure: Computed Tomography
* Drug: Docetaxel
* Radiation: Fludeoxyglucose F-18
* Drug: Gemcitabine Hydrochloride
* Drug: Pemetrexed Disodium
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have stage IIIA non-small cell lung cancer (T1-3N2) per American Joint Committee on Cancer (AJCC) 7th edition and must be considered to be surgically resectable Patients must be assessed by surgeons and are considered surgically resectable Mediastinal nodal metastases (N2) disease must be confirmed histologically Easter Cooperative Oncology Group (ECOG) performance status 0 or 1 Required imaging studies obtained within four weeks prior to registration White blood cell (WBC) >= 4000 mm^3 or granulocyte count at least 2,000/mm^3 Platelets >= 100,000/mm^3 Hemoglobin >= 10.0g/dL Total bilirubin < 1.5 mg/dL Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 3 x upper limit of normal (ULN) Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN Alkaline phosphatase < 3 x ULN Calculated/estimated or measured creatinine clearance at least 50 ml/min; note: creatinine clearance should be calculated using the Cockcroft-Gault formula; patients who will receive pemetrexed/cisplatin therapy must be obtained within 2 weeks of registration Patients cannot have hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years of registration; (prior surgery, biologic therapy, hormonal therapy, or radiation therapy for a malignancy over 5 years prior to enrollment that is not considered cured is acceptable) Patients must not have any history of other cancer within 5 years from registration with the exception of in situ carcinoma of the cervix, in situ carcinoma of the breast or completely resected non-melanoma skin cancer Patients may not have received prior chemotherapy or radiation therapy for lung cancer Patients with a history of myocardial infarction are eligible if the event occurred > 6 months prior to entry Patients must not have any clinically significant ongoing, active or serious infection, symptomatic or uncontrolled congestive heart failure, active angina, symptomatic or uncontrolled cardiac arrhythmia or any other medical condition or psychiatric illness/social situations that would limit compliance with study requirements Patents must have no contraindication to cisplatin chemotherapy including no clinically significant hearing loss unless willing to accept the potential of further loss of hearing, no symptomatic peripheral neuropathy Women must not be pregnant or breast-feeding All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study Patients must not have received any study therapies prior to registration Pemetrexed/cisplatin therapy; note: patients who will receive pemetrexed/cisplatin therapy must meet all eligibility criteria below: Patients assigned to pemetrexed/cisplatin therapy must NOT have squamous cell histology Calculated creatinine clearance must be obtained within 2 weeks of registration and calculated creatinine clearance (CrCl) must be >= 45mL/min using the standard Cockcroft and Gault formula, or the measured glomerular filtration rate (GFR) using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl Patients should have no contraindications for FDG-PET/CT

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (18F-FDG PET/CT)<br>Patients undergo fludeoxyglucose F-18 PET/CT at baseline and after course 1 of chemotherapy. Patients undergo 1 of 3 chemotherapy regimens at the discretion of the investigator. CHEMOTHERAPY REGIMEN 1: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, and 8. Patients also receive cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 3: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. | Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Procedure: Computed Tomography<br>* Undergo 18F-FDG PET/CT<br>* Other names: tomography;Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Radiation: Fludeoxyglucose F-18<br>* Undergo 18F-FDG PET/CT<br>* Other names: Fluorodeoxyglucose F18;Drug: Gemcitabine Hydrochloride<br>* Given IV<br>* Other names: LY-188011;Drug: Pemetrexed Disodium<br>* Given IV<br>* Other names: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt;Procedure: Positron Emission Tomography<br>* Undergo 18F-FDG PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of mediastinal downstaging | The predictive accuracy of the percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes will be estimated by the area under a receiver operating characteristic (ROC) curve (AUC) with a 95% confidence interval (CI). The AUC will be estimated empirically. The reference standard for the ROC analysis will be the presence or absence of mediastinal downstaging, as assessed by thoracotomy, mediastinoscopy, mediastinotomy, endoscopic bronchoscopic ultrasound (EBUS), or endoscopic ultrasound (EUS). | Up to 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of SUVmax | The predictive accuracy of the change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes will be estimated by the ROC AUC with a 95% CI. The AUC will be estimated empirically. | Baseline to 3 weeks | 
| Overall survival | Time-dependent ROC analysis will be used to determine the predictive accuracy of percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal to predict overall survival. | Up to 5 years | 
| Percent change of metabolic tumor volume | The predictive accuracy of percent change of metabolic tumor volume from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically. | Baseline to 3 weeks | 
| Percent change of SUVpeak | The predictive accuracy of percent change of SUVpeak from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically. | Baseline to 3 weeks | 
| Percent change of TLG | The predictive accuracy of percent change of TLG from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically. | Baseline to 3 weeks | 
| SUVmax | The predictive accuracy of SUVmax at T1 will be estimated by the ROC AUC with a 95% CI. The AUC will be estimated empirically. | At 3 weeks |