Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To evaluate the safety of adding oral soy isoflavone to concurrent chemotherapy and
radiotherapy for the treatment of patients with unresectable stage III non-small cell lung
cancer (NSCLC).

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

GROUP I (SQUAMOUS CELL HISTOLOGY): Patients receive etoposide intravenously (IV) over 1 hour
on days 1-5 and 29-33, cisplatin IV over 1 hour on days 1, 8, 29, and 36, and undergo
radiation therapy (RT) 5 days a week for 6.6 weeks. Within 48 hours of initiating treatment,
patients receive soy isoflavones orally (PO) daily on days 1-90.

GROUP II (NON-SQUAMOUS CELL HISTOLOGY): Patients receive pemetrexed disodium IV over 10
minutes on days 1, 22, and 43 and cisplatin IV over 1 hour on days 1, 22, and 43. Patients
also undergo RT and receive soy isoflavones as in Group I.

After completion of study treatment, patients are followed up at 4 weeks and then every 4
months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Inclusion Criteria:

- Histologic or cytologic diagnosis of stage III non-small cell lung cancer; patients
will need to meet the following criteria for stage IIIA or IIIB diagnosis:

- IIIA

- Histologic or cytologic diagnosis of ipsilateral mediastinal lymph node
involvement, or

- Tumors greater than 7 cm or with chest wall invasion, or involvement of one
of the following diaphragm, phrenic nerve, mediastinal pleura or parietal
pericardium with hilar or mediastinal lymph node involvement

- More than one mediastinal lymph node enlarged on computed tomography (CT)
scan and the same lymph nodes positive on positron emission tomography
(PET) scans or

- Paralyzed left vocal cord with separate lung primary distinct from the
aorto-pulmonary lymph nodes on the CT scan

- IIIB

- Histologic or cytologic diagnosis of N3 lymph node involvement; or

- Enlarged N3 lymph nodes on CT scan that are positive on PET scan as well;
patient must not have extension of lymph node involvement to cervical lymph
nodes other than supraclavicular lymph nodes; or

- Right sided primary with left vocal cord paralysis; or

- Evidence of tumor extension into the mediastinum and/or mediastinal
structures either at the time of mediastinoscopy, bronchoscopy or on CT
scans

- Patients with a nodules in the same lung but no other areas of involvement

- Patients with prior surgically resected stage I NSCLC who did not receive
any adjuvant therapy, who now have stage IIIA or B NSCLC will be eligible

- Southwestern Oncology Group (SWOG) performance status 0 or 1

- Absolute neutrophil count of > 1.5 x 10^9/L

- Platelet count > 100,000 x 10^9/L

- Serum creatinine =< 1.5 times the institutional upper limit of normal (ULN)

- Calculated creatinine clearance (Cockcroft-Gault formula) of >= 45mL/min

- Serum bilirubin > ULN

- Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate
pyruvate transaminase [SGPT]) > 1.5 times institutional ULN

- Alkaline phosphatase >= 2.5 times ULN

- Forced expiratory volume in one second (FEV1) of >= 1 liter and diffusion capacity of
carbon monoxide (DLCO) >= 40% of predicted

- Patient should undergo brain imaging (CT scan or magnetic resonance imaging [MRI ])
to rule out brain metastases

- Signed informed consent that details the investigational nature of the study
according to institutional and federal guidelines

- Registered with Clinical Trials Office at Karmanos Cancer Institute/Wayne State
University

Exclusion Criteria:

- Prior chemotherapy, radiation for any malignancy in which they received any thoracic
radiotherapy

- Patients with concurrent malignancy; patients with prior or concurrent malignancy
will be allowed as long as the treating physician considers it unlikely to impact the
clinical outcome of the patient

- Patients with peripheral neuropathy > 2

- Serious medical illness including but not limited to uncontrolled congestive heart
failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6
months of registration, history of chronic active hepatitis or history of human
immunodeficiency virus (HIV) or an active bacterial infection will not be eligible

- Inability or unwillingness to take folic acid or vitamin B12 or dexamethasone

- Pregnant or lactating women; all pre-menopausal and peri-menopausal women should have
a urine test for pregnancy within a week of starting therapy; all patients of child
bearing potential should agree to use an effective contraceptive method

- Patients should not participate in any other therapeutic investigational study while
taking part in this study

- Patients on warfarin will not be allowed on the study; patient on low molecular
heparin or anti direct factor Xa inhibitor (Xa) drugs will be allowed

- Patients with a soy allergy will be excluded