This phase II trial studies how well giving a hypofractionated boost to the primary tumor before standard chemotherapy and radiation therapy works in treating patients with stage II or III non-small cell lung cancer that cannot be removed by surgery. Advances in radiation oncology have allowed better radiation targeting which may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells. Giving more precise and targeted radiation before standard chemotherapy and radiation therapy may kill more tumor cells and prevent the cancer from coming back in the location in which it started.
PRIMARY OBJECTIVES: I. To estimate the primary tumor control rate at 12 months. SECONDARY OBJECTIVES: I. To further establish safety and tolerability of this regimen. II. To estimate the rates of regional, distant control as well as progression-free survival and overall survival. III. To evaluate the objective response rate (ORR) to this regimen. IV. To evaluate the response of tumors to stereotactic (high-dose) radiation using magnetic resonance tumor perfusion imaging modalities (magnetic resonance \[MR\]-dynamic contrast-enhanced \[DCE\]/perfusion weighted imaging \[PWI\], MR-diffusion, blood oxygenation level dependent \[BOLD\] sequences). OUTLINE: Patients will receive a hypofractionated boost to the primary tumor over 2 fractions (at least 40 hours apart) during week 1. Beginning week 2, patients receive cisplatin intravenously (IV) on days 8, 15, 36, and 43; and etoposide IV over 60 minutes on days 8-12 and 36-40. If carboplatin and paclitaxel is administered concurrently with radiotherapy, 2 cycles of carboplatin (AUC=6 mg/min/mL IV on day 1, 22) and paclitaxel (200 mg/m2 IV on day 1, 22) consolidation chemotherapy are required, to be administered starting 4-6 weeks after concurrent chemoradiation has ended. Each cycle is 21 days long. If cisplatin and etoposide is administered concurrently with radiotherapy, consolidation chemotherapy is not allowed. Patients also undergo standard conformal radiation therapy once daily (QD) 5 days a week for a total of 30 fractions. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Radiation boost in week 1 (days 1-5)
Given IV
Given IV
Undergo 3-dimensional conformal radiation therapy
Correlative studies
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Primary Tumor Control Rate, as Measured From the Time of Treatment Completion Until the First Documented Date of Local Failure
Primary tumor control rate at 12 months, as well its 95% confidence interval, will be reported for all eligible subjects received treatment.
Time frame: At 12 months following chemo/radiation therapy
Number of Adverse Events
Number of all adverse events with special attention to grade 3-5 esophagitis, pneumonitis, and cardiac adverse events as defined by the National Cancer Institution Common Terminology Criteria for Adverse Events CTCAE version 5.0
Time frame: Up to 30 days after completion of treatment, up to 5 years
Tolerability Measured by the Number of Patients Who Discontinue Treatment
The number of patients who discontinue treatment will be summarized.
Time frame: Up to 5 years
Regional Control
Regional control rate at 24 months will be reported for all eligible patients who received treatment.
Time frame: Up to 24 months
Distant Control
Distant control rate at 24 months will be reported for all eligible patients who received treatment
Time frame: Up to 24 months
Disease-free Survival (DFS)
Kaplan-Meier (K-M) analysis will be used to estimate DFS.
Time frame: From date of treatment initiation to progression, assessed up to 24 months
Overall Survival (OS)
K-M analysis will be used to estimate OS.
Time frame: Up to 24 months
Objective Response Rate as Measured by Response Evaluation Criteria in Solid Tumors Criteria
Objective response rate will be reported for all eligible patients who receive treatment.
Time frame: At 3 months and 6 months
Changes in Tumor Perfusion Measured by MR-DCE/PWI Amp and Kep
Changes in perfusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test. The following pharmacokinetic parameters will be used (parameters were derived using the modified Brix's model): Amp, Kep.
Time frame: Baseline to the end of week 1
Changes in Tumor Perfusion Measured by MR-DCE/PWI Kpe and Kel
Changes in perfusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test. The following pharmacokinetic parameters will be used (parameters were derived using the modified Brix's model): Kpe, Kel.
Time frame: Baseline to the end of week 1
Changes in Diffusion Measured by MR-diffusion
Changes in diffusion will be tested by comparing mean values of Apparent Diffusion Coefficient (ADC \[× 10-3 mm2/s\]) pre- and post-hypofractionated boost radiation using a paired t-test.
Time frame: Baseline to the end of week 1
Changes in Hypoxia Measured by BOLD Sequences
Changes in hypoxia will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Time frame: Baseline to the end of week 1
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