Study of Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy in Patients With Stage III Non-small Cell Lung Cancer

Official Title

Randomized Phase II Trial of Individualized Adaptive Radiation Therapy Using During-Treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-small Cell Lung Cancer (NSCLC)

Summary:

This randomized phase II trial studies how well positron emission tomography (PET)/computed tomography (CT)-guided radiation therapy works compared to standard radiation therapy in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumour cells. Using imaging procedures, such as PET and CT scans, to guide the radiation therapy, may help doctors deliver higher doses directly to the tumour and cause less damage to healthy tissue.

Trial Description

Primary Outcome:

  • Local-regional, progression-free (LRPF) rate (NRG)
  • Relative change in SUV peak from the baseline to the during-treatment FDG-PET/CT to LRPF (ECOG-ACRIN)
Secondary Outcome:
  • Baseline FMISO uptake (tumour-to-blood pool ratio) association with LRPF (i.e. the assessment of using baseline FMISO-PET uptake as a prognostic marker) (ECOG-ACRIN)
  • Change in metabolic tumour volume (ECOG-ACRIN)
  • Change of peak SUVs for FDG from pre- to during-treatment (ECOG-ACRIN)
  • FMISO total hypoxic volume (ECOG-ACRIN)
  • FMISO tumour-to-blood pool ratio (ECOG-ACRIN)
  • Incidence of grade 3+ esophagitis or cardiac adverse events related to chemoradiation between a conventional RT plan and a PET/CT-guided adaptive RT plan, as measured by Common Terminology Criteria for Adverse Events, version 4 (NRG)
  • Lung cancer cause-specific survival (NRG)
  • Max SUV or change of max SUVs for FDG from pre- to during-treatment (ECOG-ACRIN)
  • Optimal threshold for differentiating responders from non-responders (ECOG-ACRIN)
  • OS (NRG)
  • PFS (NRG)
  • Prediction of OS, LRPF, and lung cancer cause-specific survival (ECOG-ACRIN)
  • Radiation-induced lung toxicity (NRG)
  • Relative change in SUV peak from the baseline to the during-treatment FDG PET/CT and/or the baseline FMISO uptake (tumour-to-blood pool ratio) prediction of the differential benefit of the adaptive therapy (ECOG-ACRIN)
  • Time to local-regional progression (NRG)
PRIMARY OBJECTIVES:
I. To determine whether tumour dose can be escalated to improve the freedom from local-regional progression-free (LRPF) rate at 2 years when an individualized adaptive radiation treatment (RT) plan is applied by the use of a fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scan acquired during the course of fractionated RT in patients with inoperable stage III non-small cell lung cancer (NSCLC). (National Surgical Adjuvant Breast and Bowel Project [NSABP], Radiation Therapy Oncology Group [RTOG], Gynecologic Oncology Group [GOG] [NRG] Oncology) II. To determine whether the relative change in standard uptake value (SUV) peak from the baseline to the during-treatment FDG-PET/CT, defined as (during-treatment SUVpeak
  • baseline SUVpeak)/baseline SUV peak x 100%, can predict the LRPF rate with a 2-year follow up. (Eastern Cooperative Oncology Group [ECOG]-American College of Radiology Imaging Network [ACRIN]) SECONDARY OBJECTIVES:
    I. To determine whether an individualized dose escalation improves overall survival (OS), progression-free survival (PFS), lung cancer cause-specific survival, and delays time to local-regional progression compared to a conventional RT plan. (NRG Oncology) II. To compare the rate of severe (grade 3+ Common Terminology Criteria for Adverse Events [CTCAE], v. 4) radiation-induced lung toxicity (RILT) defined as severe RILT pneumonitis or clinical fibrosis. (NRG Oncology) III. To compare other severe adverse events, including grade 3+ (CTCAE, v. 4) esophagitis or grade 2 pericardial effusions, or any grade cardiac adverse events related to chemoradiation between a PET/CT-guided adaptive approach and a conventional RT plan. (NRG Oncology) IV. To evaluate the association of baseline 18F-fluoromisonidazole (FMISO), a PET/CT imaging agent uptake (tumour-to-blood pool ratio) with LRPF (i.e., the assessment of using baseline FMISO-PET uptake as a prognostic marker). (ECOG-ACRIN) V. To determine if the relative change in SUVpeak from baseline to during-treatment FDG-PET/CT and/or baseline FMISO uptake (tumour-to-blood pool ratio) predicts the differential benefit of the adaptive therapy, i.e., the association of uptake parameters with LRPF rate depending on the assigned treatment thus, assessing if these uptake parameters can be useful in guiding therapies, i.e., predictive markers. (ECOG-ACRIN) VI. To determine if other PET-imaging uptake parameters (SUV peak during-treatment for FDG-PET, maximum SUV, or relative change of maximum SUVs from pre- to during-treatment FDG-PET/CT, change in metabolic tumour volume, FMISO total hypoxic volume, FMISO tumour to mediastinum ratio, EORTC or University of Michigan/Kong's response criteria) will predict OS, LRPF rate, and lung cancer cause-specific (LCS) survival as well as to explore the optimal threshold for differentiating responders from non-responders. (ECOG-ACRIN) TERTIARY OBJECTIVES:
    I. To study whether a model of combining current clinical and/or imaging factors with blood markers, including osteopontin (OPN) [for hypoxia marker], carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1 (for tumour burden), and interleukin (IL)-6 (inflammation) will predict the 2-year LRPF rate and survival better than a current model using clinical factors and radiation dose as well as imaging factors. II. To determine/validate whether a model of combining mean lung dose (MLD), transforming growth factor beta1 (TGF beta1) and IL-8 will improve the predictive accuracy for clinical significant RILT better comparing to the current model of using MLD alone. III. To explore, in a preliminary manner, whether proteomic and genomic markers in the blood prior to and during the early course of treatment are associated with tumour response after completion of treatment, LRPF rate, PFS, OS, and pattern of failure and treatment-related adverse events, such as radiation pneumonitis, esophagitis, and pericardial effusion. (exploratory)
OUTLINE:

Prior to treatment, patients undergo fludeoxyglucose F 18 (FDG) positron emission tomography (PET) and computed tomography (CT) scans at baseline and periodically during study. A subset of patients also undergo 18F-fluoromisonidazole PET/CT scan at baseline. Patients are randomized to 1 of 2 treatment arms: ARM I (standard chemoradiotherapy): Patients undergo radiation therapy once daily (QD) 5 days a week for 30 fractions. Patients also receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes once weekly for 6 weeks. Patients undergo FDG-PET/CT imaging between fractions 18 and 19. ARM II (experimental chemoradiotherapy): Patients undergo an individualized dose of image-guided radiation therapy QD 5 days a week for 30 fractions and undergo 18 F FDG-PET/CT between fractions 18 and 19. Based on the scan results, patients undergo individualized adaptive radiation therapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I. CONSOLIDATION CHEMOTHERAPY: Beginning 4-6 weeks after chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 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 at 1 month, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

View this trial on ClinicalTrials.gov

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Resources

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