- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03110978
Stereotactic Body Radiation Therapy With or Without Nivolumab in Treating Patients With Stage I-IIA or Recurrent Non-small Cell Lung Cancer
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
Study Overview
Status
Conditions
- Lung Non-Small Cell Squamous Carcinoma
- Stage IIA Lung Cancer AJCC v8
- Neuroendocrine Carcinoma
- Lung Atypical Carcinoid Tumor
- Minimally Invasive Lung Adenocarcinoma
- Lung Neuroendocrine Neoplasm
- Stage I Lung Cancer AJCC v8
- Stage IA1 Lung Cancer AJCC v8
- Stage IA2 Lung Cancer AJCC v8
- Stage IA3 Lung Cancer AJCC v8
- Stage IB Lung Cancer AJCC v8
- Recurrent Lung Non-Small Cell Carcinoma
- Recurrent Lung Adenocarcinoma
- Recurrent Lung Large Cell Carcinoma
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Conroe, Texas, United States, 77384
- MD Anderson in The Woodlands
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
Houston, Texas, United States, 77079
- MD Anderson West Houston
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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,
- Second tumor in different lobe or lung,
- Tumor-free interval of at least 4 years (y)
- Patient with multiple primary lung tumors who will receive multiple courses of stereotactic body radiation therapy (SBRT) (50Gy in 4Fx or 70Gy in 10Fx) are eligible
Patients with isolated lung parenchymal recurrent/persistent NSCLC (histology as defined in eligibility criterion 1) after prior definitive surgery or radiotherapy/chemotherapy, when the lesion or lesions are suitable for SABR, are also eligible.
- Patients with a single metastatic focus in the lung parenchyma with no other lesions are also eligible, because this presentation is challenging to distinguish from recurrent disease.
- Recurrent disease can be in the same lobe or a different lobe but should not invade critical structures (esophagus, brachial plexus, major vessels, heart, spinal cord); should not involve any lymph node; and should not include any other suspicious lesions in the lung or any other locations.
- Any prior therapy (surgery, radiotherapy, or systemic) must have been completed at least 12 weeks before administration of the study drug.
- Tumors should be =< 7 cm (measured by CT imaging in the lung window setting) with N0M0; PET) imaging is required for restaging (per eligibility criterion) and any lymph node suspected of harboring tumor should be confirmed by biopsy (per eligibility criterion)
- Both Chest CT and PET/CT are required within 16 weeks and at least one of them needs to be done within 12 weeks (plus/minus 1 week). Any lymph node suspected of harboring disease based on its shape, size, or PET standardized uptake value (SUV) should be discussed by treating physician and diagnostic radiologist
Patients with medically inoperable stage I disease (T1 or T2a [tumor size =< 5 cm] N0M0) or selected stage IIa disease (T2 [tumor size > 5 cm but =< 7 cm] N0M0) who have poor lung function or other significant cardiovascular or other comorbidity such as diabetes are eligible. Patients with operable disease who choose to have SABR are also eligible.
- The standard justification for medical inoperability is based on pulmonary function and can include any of the following: baseline forced expiratory volume in 1 second (FEV1) < 50% of predicted value; diffusion capacity < 50% of predicted value; baseline hypoxemia or hypercapnia; exercise oxygen consumption < 50% of predicted value; severe pulmonary hypertension; severe cerebral, cardiac, or peripheral vascular disease; and severe chronic heart disease
- Patients must have a Zubrod performance status score of 0-2 (2 is included here because such patients are typically > 70 years old and cannot tolerate surgery)
The following mandatory staging studies must be done within 12 weeks before study registration:
- Chest CT or PET/CT scans of both lungs, the mediastinum, adrenal glands and rest of the body; primary tumor dimension will be measured on diagnostic CT and again on simulation CT using the lung window setting.
- Mediastinoscopy or endobronchial ultrasound-guided biopsy of the mediastinal lymph nodes is recommended and required for any patients with PET/CT or CT findings suggesting lymph node involvement.
- Brain magnetic resonance imaging (MRI) or CT scan if symptoms or signs suggest brain metastases.
- Invasive mediastinal staging: For all patients with CT or PET evidence of hilar involvement (level 10) or with mediastinal lymph nodes > 1.0 cm in the shortest diameter or clinically suspicious by treating physician and/or radiologist, disease must be staged by cervical mediastinoscopy, esophageal endoscopic ultrasound-guided biopsy, or endobronchial ultrasound-guided biopsy
For patients with left-sided tumors and enlarged nodes (> 1.0 cm in the shortest diameter) on the aortopulmonary window setting, the aortopulmonary nodes must be biopsied by extended mediastinoscopy, Chamberlain procedure, video-assisted thoracoscopic surgery (VATS) approach, or ultrasound-guided biopsy to ensure that the patient does not have N2 disease. At the time of cervical mediastinoscopy, esophageal endoscopic ultrasound-guided biopsy, or endobronchial ultrasound-guided biopsy, the following nodal stations must be examined and biopsied, if present:
- Ipsilateral nodal station 4
- Contralateral nodal station level 4, and
- Subcarinal nodes (level 7) For left-sided tumors, any lymph node in the superior or anterior mediastinum > 1.0 cm in the shortest axis on CT or positive on PET must be identified and biopsied. Eligibility requires that any PET-positive mediastinal or distant sites must be biopsy-negative. However, if the treating physician and diagnostic radiologist strongly suspect PET positivity, the patient should not be enrolled even if the biopsy is negative (to exclude patients with false-negative biopsy)
- All patients must sign a study-specific consent form
All patients (men & women) of childbearing potential should use a method of birth control that is effective for them throughout their participation in this study.
- Women of childbearing potential should use an adequate contraceptive method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug; must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours before the start of nivolumab; and must not be breastfeeding.
- Men who are sexually active with women of childbearing potential must use a contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab will be instructed to use contraception for 7 months after the last dose of nivolumab.
- Women who are not of childbearing potential (i.e. are postmenopausal or surgically sterile) & azoospermic men do not require contraception
- White blood cell (WBC) >= 2000/uL (within 30 days before study registration)
- Neutrophils (Neuts) >= 1500/uL (within 30 days before study registration)
- Platelets (PLT) >= 100 x 10^3/uL (within 30 days before study registration)
- Hemoglobin (HGB) > 9.0 g/dL (within 30 days before study registration)
- Serum creatinine =< 2 x upper limit of normal (ULN) or creatinine clearance (calculated with the Cockcroft-Gault formula) >= 30 mL/min (within 30 days before study registration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (within 30 days before study registration)
- Total bilirubin (Bili T) =< 1.5 x ULN (although patients with Gilbert syndrome can have total bilirubin < 3.0 mg/dL (within 30 days before study registration)
Exclusion Criteria:
- 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
Patients with allergies or adverse drug reactions to the following are not eligible:
- History of allergy to study drug components;
- History of severe hypersensitivity reaction to any monoclonal antibody
- Patients who have had prior treatment with an anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways are not eligible
- Patients are known to have contraindications to radiotherapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (stereotactic body radiation therapy)
Patients undergo stereotactic body radiation therapy over 1-2 weeks.
|
Undergo stereotactic body radiation therapy
Other Names:
|
Experimental: 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.
|
Given IV
Other Names:
Undergo stereotactic body radiation therapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival with events defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy (including lung cancer), and death
Time Frame: 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.
|
From the randomization date, assessed up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 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.
|
From the randomization date assessed up to 5 years
|
Incidence of adverse events related to stereotactic body radiation therapy and immunotherapy
Time Frame: Up to 5 years
|
Will be summarized by frequency tables.
The association between the types and severity of toxicity and the treatment groups will be evaluated.
No formal statistical testing will be performed on these summary data.
|
Up to 5 years
|
Immunologic markers analyses
Time Frame: Up to 5 years
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Joe Y Chang, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neoplasms, Squamous Cell
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Recurrence
- Adenocarcinoma
- Carcinoma, Squamous Cell
- Carcinoma, Neuroendocrine
- Neuroendocrine Tumors
- Adenocarcinoma of Lung
- Carcinoma, Large Cell
- Carcinoid Tumor
- Adenocarcinoma, Bronchiolo-Alveolar
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- 2016-0737 (Other Identifier: M D Anderson Cancer Center)
- NCI-2018-01212 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lung Non-Small Cell Squamous Carcinoma
-
National Cancer Institute (NCI)Active, not recruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Unresectable Lung Non-Small Cell Carcinoma | Unresectable Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic...United States
-
National Cancer Institute (NCI)Active, not recruitingStage IIIA Lung Non-Small Cell Cancer AJCC v7 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IV Lung Non-Small Cell Cancer AJCC v7 | Stage III Lung Non-Small Cell Cancer AJCC...United States
-
National Cancer Institute (NCI)RecruitingStage IV Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Recurrent Lung Non-Squamous Non-Small Cell CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedMetastatic Lung Non-Squamous Non-Small Cell Carcinoma | Recurrent Lung Non-Squamous Non-Small Cell Carcinoma | Stage IV Lung Non-Small Cell Cancer AJCC v7United States
-
National Cancer Institute (NCI)RecruitingLung Non-Small Cell Carcinoma | Lung Non-Small Cell Squamous Carcinoma | Lung Non-Squamous Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8United States, Guam
-
Western Regional Medical CenterTerminatedNon-squamous Cell Non-Metastatic Non-Small Cell Lung Cancer | Squamous Cell Non-Metastatic Non-Small Cell Lung CancerUnited States
-
Peking University First HospitalMerck Sharp & Dohme LLCNot yet recruitingAdvanced Non-squamous Non-small-cell Lung Cancer | Metastatic Non-squamous Non Small Cell Lung Cancer | Recurrent Non-Squamous Non-Small Cell Lung CancerChina
-
AIO-Studien-gGmbHAstraZenecaTerminatedNSCLC | Non-squamous Non-small Cell Lung Cancer Stage II | Non-squamous Non-small Cell Lung Cancer Stage IIIA | Non-squamous Non-small Cell Lung Cancer Stage IIIB | Activating EGFR MutationGermany
-
National Cancer Institute (NCI)Active, not recruitingStage IV Lung Cancer AJCC v8 | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Recurrent Lung Non-Squamous Non-Small Cell CarcinomaUnited States
-
Bristol-Myers SquibbNo longer availableNon-squamous Non-Small Cell Lung Cancer | Squamous Non-Small Cell Lung CancerBrazil, Canada
Clinical Trials on Nivolumab
-
Universitair Ziekenhuis BrusselNot yet recruiting
-
Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...Terminated
-
Bristol-Myers SquibbRecruitingMelanomaSpain, United States, Italy, Chile, Greece, Argentina
-
Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminatedRecurrent GlioblastomaUnited States
-
Jason J. Luke, MDArray BioPharmaActive, not recruitingMelanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
HUYABIO International, LLC.Bristol-Myers SquibbRecruitingUnresectable or Metastatic Melanoma | Progressive Brain MetastasisSpain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
-
Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActive, not recruitingAdvanced Renal Cell CarcinomaUnited States
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
IRCCS San RaffaeleBristol-Myers SquibbRecruiting
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan