Hypofractionated Radiotherapy With Carboplatin and Paclitaxel in Non-Small Cell Lung Cancer

This study is designed to evaluate the feasibility of hypofractionated IMRT to 62.5 Gy in 25
fractions (2.5 Gy/fraction) with 4D PET/CT-based radiation treatment planning and concurrent
carboplatin and paclitaxel in Stage IIIA or Stage IIIB NSCLC subjects.

Hypofractionated IMRT allows escalation of the biological effective dose (BED) to the tumor
and reduces the radiation treatment duration to 5 weeks. Increasing the BED without
protracting the RT course may be a more effective means of dose escalation than simply
increasing the total dose but using only 2 Gy/fraction, as was tested in RTOG 0617.

Investigators require the use of advanced treatment planning techniques, including 4D CT
simulation, volume delineation utilizing PET/CT to identify gross disease and IMRT to
minimize the total volume of normal tissue receiving a high dose of radiation.

As minimal published work has evaluated hypofractionated RT regimens for Stage III NSCLC with
concurrent chemotherapy, investigators selected a moderately escalated dose/fraction of 2.5
Gy for evaluation in combination with concurrent carboplatin and paclitaxel.

Inclusion Criteria:

- Pathologically proven diagnosis of Stage IIIA or IIIB non-small cell lung cancer
(NSCLC).

- Stage IIIA subjects who are considered eligible for resection following neoadjuvant
chemoradiation are eligible for this study.

- No PET/CT evidence of metastatic disease.

- An MRI of the brain with contrast excluding intracranial metastatic disease (or CT
with contrast if MRI is medically contraindicated). An MRI without contrast is only
permitted if the subject cannot have contrast for medical reasons.

- If a pleural effusion is present, it must be tapped and confirmed to be cytologically
negative. If an effusion is deemed too small to safely tap, the subject will be
eligible.

- Subjects must have measurable or evaluable disease.

- No prior thoracic radiotherapy.

- Age > 18 years at time of registration.

- ECOG Performance Status of 0-2 (Karnofsky performance scale ≥ 60).

- Hgb > 9 g/dL; ANC (absolute neutrophil count) > 1500/µl; platelets > 100,000 mcL.

- Subjects must sign study-specific informed consent form prior to registration.

- Radiation therapy and chemotherapy must start within 4 weeks of study enrollment.

Exclusion Criteria:

- Evidence of severe or uncontrolled psychiatric or systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease) that would interfere
with study protocol as judged by the investigator.

- Active connective tissue disorders, such as active lupus or scleroderma.

- Known Acquired Immune Deficiency (HIV (+)/AIDS).

- Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regiment to harm nursing infants. Women of
childbearing potential must agree to use medically approved and adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.