Randomized Phase II Trial of Individualized Adaptive Radiotherapy Using During-Treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 62
- 主要终点
- Local-regional, progression-free (LRPF) rate (National Surgical Adjuvant Breast and Bowel Project [NSABP], Radiation Therapy Oncology Group [RTOG], Gynecologic Oncology Group [GOG] [NRG])
研究概览
简要总结
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 tumor cells. Using imaging procedures, such as PET and CT scans, to guide the radiation therapy, may help doctors deliver higher doses directly to the tumor and cause less damage to healthy tissue.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether tumor 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 (tumor-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 (tumor-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 tumor volume, FMISO total hypoxic volume, FMISO tumor 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)
CORRELATIVE SCIENCE OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have FDG-avid (maximum SUV >= 4.0) (from PET scan of any date, any scanner) and histologically or cytologically proven non-small cell lung cancer
- •Patients must be clinical American Joint Committee on Cancer (AJCC) stage IIIA or IIIB (AJCC, 7th ed.) with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team, involving evaluation by at least 1 thoracic surgeon within 8 weeks prior to registration; Note: For patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and a medical oncologist, or pulmonologist
- •Patients with multiple, ipsilateral pulmonary nodules (T3 or T4) are eligible if a definitive course of daily fractionated radiation therapy (RT) is planned
- •History/physical examination, including documentation of weight, within 2 weeks prior to registration
- •FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration
- •CT scan or sim CT of chest and upper abdomen (IV contrast is recommended unless medically contraindicated) within 6 weeks prior to registration
- •CT scan of the brain (contrast is recommended unless medically contraindicated) or MRI of the brain within 6 weeks prior to registration
- •Pulmonary function tests, including diffusion capacity of carbon monoxide (DLCO), within 6 weeks prior to registration; patients must have forced expiratory volume in 1 second (FEV1) >= 1.2 Liter or >= 50% predicted without bronchodilator
- •Zubrod performance status 0-1
- •Able to tolerate PET/CT imaging required to be performed at an American College of Radiology (ACR) Imaging Core Laboratory (Lab) qualified facility
- •Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 2 weeks prior to registration on study)
- •Platelets >= 100,000 cells/mm^3 (within 2 weeks prior to registration on study)
- •Hemoglobin (Hgb) >= 10.0 g/dL (note: the use of transfusion or other intervention to achieve Hgb >= 10.0 g/dL is acceptable) (within 2 weeks prior to registration on study)
- •Serum creatinine within normal institutional limits or a creatinine clearance >= 60 ml/min within 2 weeks prior to registration
- •Negative serum or urine pregnancy test within 3 days prior to registration for women of childbearing potential
- •Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study
- •The patient must provide study-specific informed consent prior to study entry
排除标准
- •Patients with any component of small cell lung carcinoma are excluded
- •Patients with evidence of a malignant pleural or pericardial effusion are excluded
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- •Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- •Transmural myocardial infarction within the last 6 months
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- •Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- •Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite attempts to improve glucose control by fasting duration and adjustment of medications; patients with diabetes will preferably be scheduled in the morning and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians
- •Patients with T4 disease with radiographic evidence of massive invasion of a large pulmonary artery and tumor causing significant narrowing and destruction of that artery are excluded
研究组 & 干预措施
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: External Beam Radiation Therapy (Radiation)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Computed Tomography (Procedure)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Image-Guided Adaptive Radiation Therapy (Radiation)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Positron Emission Tomography (Procedure)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Computed Tomography (Procedure)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Positron Emission Tomography (Procedure)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: 18F-Fluoromisonidazole (Drug)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: 18F-Fluoromisonidazole (Drug)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Carboplatin (Drug)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Fludeoxyglucose F-18 (Drug)
Arm I (standard chemoradiotherapy)
Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel 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.
干预措施: Paclitaxel (Drug)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Fludeoxyglucose F-18 (Drug)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Paclitaxel (Drug)
Arm II (experimental chemoradiotherapy)
Patients undergo an individualized dose of image-guided radiotherapy 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 radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Local-regional, progression-free (LRPF) rate (National Surgical Adjuvant Breast and Bowel Project [NSABP], Radiation Therapy Oncology Group [RTOG], Gynecologic Oncology Group [GOG] [NRG])
时间窗: 2 years
Relative change in standard uptake volume (SUV) peak from the baseline to the during-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) to LRPF (ECOG-ACRIN)
时间窗: Baseline to 2 years
Percentage of Participants Alive Without Local-regional Progression [Local-regional Progression-free (LRPF) Survival] at Two Years (NRG)
时间窗: Randomization to 2 years
LRPF survival is defined as survival without local-regional progression (LRP) as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with integration of 8F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and reviewed centrally based on submitted CT scans. LRP is defined as any of the following: * ≥ 20% increase in any of the target lesions (primary and nodal disease), * ≥ 20% increase in the peak SUV of target lesions, * appearance of one or more new lesions within previously irradiated regions. LRPF-free survival time is defined as time from registration to the date of first local-regional progression, distant recurrence (censored), death without documented LRP (censored), or death. LRPF survival rates are estimated using the Kaplan-Meier method.
Relative Change in SUVpeak From the Baseline to the During-treatment Fludeoxyglucose F 18 (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) to LRPF With a 2-year Follow up. (ECOG-ACRIN)
时间窗: Baseline to during-treatment (approximately between fractions 18-19) Randomization to 2 years
To determine whether the relative change in SUVpeak (from the baseline to the during-treatment FDG-PET/CT) can predict the LRPF with a 2-year follow up. Relative ΔSUVpeak = (Mid-treatment SUVpeak - baseline SUVpeak)/baseline SUVpeak x 100 LRPF was determined from Randomization up to 2 years
次要结局
- Change of peak SUVs for FDG from pre- to during-treatment (ECOG-ACRIN)(Baseline to up to 5 years)
- Radiation-induced lung toxicity (NRG)(Up to 5 years)
- Baseline 18F-fluoromisonidazole (FMISO) uptake (tumor-to-blood pool ratio) association with LRPF (i.e. the assessment of using baseline FMISO-PET uptake as a prognostic marker) (ECOG-ACRIN)(Baseline)
- FMISO tumor-to-blood pool ratio (ECOG-ACRIN)(Up to 5 years)
- Overall survival (OS) (NRG)(Interval from registration to the date of death or censored at the date of data collection, assessed up to 5 years)
- Prediction of OS, LRPF, and lung cancer cause-specific survival (ECOG-ACRIN)(Up to 5 years)
- Optimal threshold for differentiating responders from non-responders (ECOG-ACRIN)(Up to 5 years)
- Lung cancer cause-specific survival (NRG)(Interval from the date of registration to the date of death directly from lung cancer, or censored at the last date of data collection if still alive, assessed up to 5 years)
- Time to local-regional progression (NRG)(Interval from registration to date of local or regional progression, assessed up to 5 years)
- Progression free survival (PFS) (NRG)(Interval from the date of registration to the date of tumor progression locally, regionally, distantly, or death, whichever occurs first, or censored at the last date of data collection, assessed up to 5 years)
- 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 and 5 (NRG)(Up to 5 years)
- Relative change in SUV peak from the baseline to the during-treatment FDG PET/CT and/or the baseline FMISO uptake (tumor-to-blood pool ratio) prediction of the differential benefit of the adaptive therapy (ECOG-ACRIN)(Baseline to up to 5 years)
- Max SUV or change of max SUVs for FDG from pre- to during-treatment (ECOG-ACRIN)(Baseline to up to 5 years)
- Change in metabolic tumor volume (ECOG-ACRIN)(Baseline to up to 5 years)
- FMISO total hypoxic volume (ECOG-ACRIN)(Up to 5 years)
- Percentage of Participants With Death Due to Lung Cancer (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.)
- Percentage of Participants With Local-regional Progression (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.)
- Percentage of Participants Alive (Overall Survival) (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.)
- Percentage of Participants Alive Without Progression (Progression-free Survival) (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.)
- Percentage of Participants With Grade 3+ Radiation-induced Lung Toxicity [RILT] at Any Time (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years.)
- Percentage of Participants With Grade 3+ Esophagitis, Pericardial Effusion, and Any Cardiac Adverse Events at Any Time (NRG)(From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years.)
- Baseline 18F-fluoromisonidazole (FMISO) Uptake (Tumor-to-blood Pool Ratio) Measures Association With LRPF 2-years Post Registration (ECOG-ACRIN)(Baseline and 2-years after randomization)
- Baseline 18F-fluoromisonidazole (FMISO) Tumor Hypoxic Volume Association With LRPF 2-years Post Registration (ECOG-ACRIN)(Baseline and 2-years after randomization)
- Relative Change in SUV Peak From the Baseline to the During-treatment FDG PET/CT Prediction of the Differential Benefit of the Adaptive Therapy (ECOG-ACRIN)(Baseline to up to 5 years after randomization)
- SUVmax at Baseline Prediction of OS and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔSUVmax, From Baseline to the During-treatment FDG PET/CT, to Predict OS and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- ΔSUVpeak Prediction of Overall Survival, Progression Free Survival, and Lung Cancer Cause-specific Survival (ECOG-ACRIN)(Up to 5 years)
- FDG ΔSUVpeak From Baseline to the During-treatment FDG PET/CT, to Predict Overall Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔMTV From Baseline to the During-treatment FDG PET/CT, to Predict Overall Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FMISO Hypoxic Tumor Volume (HV) @Baseline, to Predict Overall Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG SUVmax @ Baseline FDG PET/CT, to Predict Lung Cancer Cause-specific Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔSUVmax From Baseline to the During-treatment FDG PET/CT, to Predict Lung Cancer Cause-specific Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔSUVpeak From Baseline to the During-treatment FDG PET/CT, to Predict Lung Cancer Cause-specific Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔMTV From Baseline to the During-treatment FDG PET/CT, to Predict Lung Cancer Cause-specific Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FMISO Hypoxic Tumor Volume (HV) @Baseline, to Predict Lung Cancer Cause-specific Survival and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG SUVmax @ Baseline FDG PET/CT, to Predict Local-Regional Progression-Free and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔSUVmax From Baseline to the During-treatment FDG PET/CT, to Predict Local-Regional Progression-Free and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔSUVpeak From Baseline to the During-treatment FDG PET/CT, to Predict Local-Regional Progression-Free and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FDG ΔMTV From Baseline to the During-treatment FDG PET/CT, to Predict Local-Regional Progression-Free and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)
- FMISO Hypoxic Tumor Volume @Baseline, to Predict Local-Regional Progression-Free and Optimal Threshold (ECOG-ACRIN)(Baseline to up to 5 years)