Phase II Randomized Clinical Trials Comparing Immunotherapy Plus Stereotactic Ablative Radiotherapy (I-SABR) Versus SABR Alone for Stage I, Selected Stage IIa, or Isolated Lung Parenchymal Recurrent Non-Small Cell Lung Cancer: I-SABR
概览
- 阶段
- 2 期
- 干预措施
- Stereotactic Body Radiation Therapy
- 疾病 / 适应症
- 未指定
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 140
- 试验地点
- 5
- 主要终点
- Event-free survival with events defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death
- 状态
- 进行中（未招募）
- 最后更新
- 16天前
概览
简要总结
This phase II trial studies how well stereotactic body radiation therapy with or without nivolumab works in treating patients with stage I-IIA non-small cell lung cancer or cancer that has come back. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy and nivolumab may work better at treating non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVE: I. Event-free survival (EFS), with events defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death. SECONDARY OBJECTIVES: I. Overall survival (OS). II. Toxicity related to stereotactic body radiation therapy (stereotactic ablative body radiation therapy \[SABR\]) and immunotherapy. III. Exploratory analyses of potential predictive markers and immunologic mechanisms of action. EXPLORATORY/TRANSLATIONAL RESEARCH OBJECTIVES: I. Identify candidate tumor-associated antigens or genes that elicit cellular and humoral immune responses in serum samples (with Immunotherapy Platform). II. Assess PDL1 expression in tumor biopsy specimens (with Department of Pathology). III. Identify potential radiomics features from positron emission tomography (PET)/computed tomography (CT) or magnetic resonance imaging (MRI) scans that may predict treatment response and toxicity (with Department of Radiation Physics). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo stereotactic body radiation therapy over 1-2 weeks. ARM II: Patients undergo stereotactic body radiation therapy over 1-2 weeks. Beginning within 36 hours before or after the first fraction of stereotactic body radiation therapy, patients also receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles with nivolumab repeat every 4 weeks for up to 12 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, every 6 months for up to 3 years, then annually thereafter.
研究者
入排标准
入选标准
- •Histological confirmation of non-small cell lung cancer (NSCLC) by either biopsy or cytology is required for the primary diagnosis and is recommended for recurrent disease. The following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma (with or without bronchioloalveolar carcinoma features), large cell carcinoma (with or without neuroendocrine features), neuroendocrine carcinoma (either NSCLC with neuroendocrine features or atypical carcinoids, but not small cell lung carcinoma), bronchioloalveolar cell carcinoma, or non-small cell carcinoma not otherwise specified
- •Stage I or selected stage IIa according to the 7th version of the International Association for the Study of Lung Cancer (IASLC) system: stage I (T1 or T2a \[tumor size =\< 5 cm\] N0M0) stage IIa (T2 \[tumor size \> 5 cm but =\< 7 cm\] N0M0)
- •Patients with multiple primary lung tumors (defined below) are eligible:
- •Synchronous tumors (diagnosed within 6 months \[mo\]),
- •Different histology,
- •Same histology,
- •Second tumor in different lobed or lung;
- •Metachronous tumors (diagnosed \> 6 mo apart),
- •Different histology,
- •Same histology,
排除标准
- •Patients with tumors \> 7 cm or tumors involving the main bronchus or associated vessels or tumors that invade any critical structures (such as esophagus, brachial plexus, heart, mediastinal major vessels) are not suitable for SABR
- •Patients with direct evidence of regional or distant metastases after appropriate staging studies, or with synchronous non-lung primary or prior non-lung malignancy (other than nonmelanomatous skin cancer or in situ cancer) diagnosed within the past 3 years are not eligible. Patients with a history of curable non-lung cancer up to 3 years before registration and have been cancer-free for 2 years are eligible
- •Patients who have received previous immunotherapy with PD1 or CTLA4 antibodies are not eligible
- •Patients with plans to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) or other systemic therapy (including chemotherapy, target therapy and other type of immunotherapy or investigative agents) while on this protocol, except at disease progression, are not eligible
- •Female patients who are pregnant or lactating are not eligible (because treatment involves unforeseeable risks to the embryo or fetus)
- •Patients for whom SABR plans cannot meet the minimum requirement of target coverage and dose-volume constraints of critical structures (see SABR treatment planning section) are not eligible
- •Patients who have active, known, or suspected autoimmune disease are not eligible. However, patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition that requires only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- •Patients with a known history of antibodies to human immunodeficiency virus (HIV) -1 or -2 are not eligible. Patients with live vaccines
- •Patients with a known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection are not eligible
- •Patients who have a condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration are not eligible. However, inhaled or topical steroids, adrenal replacement doses, and \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
研究组 & 干预措施
Arm I (stereotactic body radiation therapy)
Patients undergo stereotactic body radiation therapy over 1-2 weeks.
干预措施: Stereotactic Body Radiation Therapy
Arm II (stereotactic body radiation therapy, nivolumab)
Patients undergo stereotactic body radiation therapy over 1-2 weeks. Beginning within 36 hours before or after the first fraction of stereotactic body radiation therapy, patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 4 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Stereotactic Body Radiation Therapy
Arm II (stereotactic body radiation therapy, nivolumab)
Patients undergo stereotactic body radiation therapy over 1-2 weeks. Beginning within 36 hours before or after the first fraction of stereotactic body radiation therapy, patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 4 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab
结局指标
主要结局
Event-free survival with events defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death
时间窗: From the randomization date, assessed up to 5 years
Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis.
次要结局
- Immunologic markers analyses(Up to 5 years)
- Overall survival(From the randomization date assessed up to 5 years)
- Incidence of adverse events related to stereotactic body radiation therapy and immunotherapy(Up to 5 years)