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

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.

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