- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04933903
BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab
January 26, 2023 updated by: Brown University
BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab for Patients With Resectable Stage IB - III Non-Small Cell Lung Cancer
This single-arm phase 2 study will enroll patients with resectable and operable stage IB - III non-small cell lung cancer and treat them with pre-operative ipilimumab + nivolumab plus low-dose stereotactic body radiation therapy (SBRT) delivered concurrently.
Only patients who proceed to surgery will be evaluable for the primary endpoint.
The primary efficacy outcome measurement will be pathologic response (including Major Pathologic Response (MPR), and Complete Pathologic Response (CPR)).
Secondary outcome measures include safety, and exploratory biomarkers of immune response in pre- and post-operative blood and tissue.
A two-stage design will stop the study if fewer than 3 of the first 9 evaluable patients do not achieve MPR.
An early stopping rule for safety will stop the study if more than 12 patients are enrolled to find the first 9 evaluable patients.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
25
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: BrUOG
- Phone Number: 401-863-3000
- Email: BrUOG@Brown.edu
Study Locations
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Recruiting
- Rhode Island Hospital
-
Contact:
- L BrUOG
- Phone Number: 401-863-3000
- Email: BrUOG@Brown.edu
-
Principal Investigator:
- Thomas A DiPetrillo, MD
-
Principal Investigator:
- Christopher G Azzoli, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Pathologically confirmed NSCLC
- Age > 18
- ECOG Performance Status 0-1.
- Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be > 0.8 L or be > 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
- Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
- N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
- Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level.
- No prior history of thoracic radiation.
Adequate Organ and marrow function as defined below
- leukocytes ≥2,000/mcL,
- absolute neutrophil count ≥1,000/mcL,
- platelets ≥100,000/mcL,
- Hemoglobin >8.0 g/dL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
- Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
- Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
- Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
Exclusion Criteria:
- Pathologically confirmed NSCLC *
- Age > 18 *
- ECOG Performance Status 0-1.
- Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be > 0.8 L or be > 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
- Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
- N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
- Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level. *
- No prior history of thoracic radiation.
Adequate Organ and marrow function as defined below
- leukocytes ≥2,000/mcL,
- absolute neutrophil count ≥1,000/mcL,
- platelets ≥100,000/mcL,
- Hemoglobin >8.0 g/dL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
- Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
- Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
- Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Protocol Therapy
Ipilimumab: 1mg/kg IV day 1.
Nivolumab: 3mg/kg IV days 1, 15, 29.
SBRT delivered as 1-2 fractions to the gross primary tumor and nodal disease following day 1 infusion and completed by day 3 (7Gy x 1; 4Gy x 2).
|
1mg/kg IV on day 1 (1 dose total)
3mg/kg (to a maximum of 240mg) IV on days 1, 15, 29 (+/- 3 days) (3 doses total)
1 fraction or 2 fractions delivered to the gross primary tumor and nodal disease, following the first treatment with ipilimumab + nivolumab on days 1-3.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients with a Pathologic Response
Time Frame: From beginning of study treatment to approximately day 49-63 on study.
|
Assess Pathologic Response (major pathologic response and complete pathologic response) following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab.
|
From beginning of study treatment to approximately day 49-63 on study.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Beginning of study treatment through 90 days post study treatment completion.
|
Assess safety and operative morbidity following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab and surgery.
|
Beginning of study treatment through 90 days post study treatment completion.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Christopher G Azzoli, MD, Brown University
- Principal Investigator: Thomas A DiPetrillo, MD, Brown University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 5, 2021
Primary Completion (Anticipated)
December 1, 2023
Study Completion (Anticipated)
January 1, 2025
Study Registration Dates
First Submitted
October 15, 2020
First Submitted That Met QC Criteria
June 14, 2021
First Posted (Actual)
June 22, 2021
Study Record Updates
Last Update Posted (Actual)
January 27, 2023
Last Update Submitted That Met QC Criteria
January 26, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- BrUOG 397
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
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 Non Small Cell Lung Cancer
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Stanford UniversityAstraZenecaRecruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Lung Cancer Stage IIUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
Clinical Trials on Ipilimumab
-
Shanghai Henlius BiotechRecruitingHealthy Male VolunteersChina
-
Takara Bio Inc.TheradexCompletedMalignant MelanomaUnited 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
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan
-
Italian Network for Tumor Biotherapy FoundationBristol-Myers SquibbUnknown
-
Gustave Roussy, Cancer Campus, Grand ParisCompleted
-
MacroGenicsCompletedMelanoma | Non Small Cell Lung CancerUnited States
-
National Cancer Institute (NCI)RecruitingGlioblastoma | Malignant Glioma | GliosarcomaUnited States
-
Ontario Clinical Oncology Group (OCOG)Bristol-Myers SquibbRecruitingMetastatic Renal Cell CarcinomaCanada, Australia
-
Bristol-Myers SquibbCompletedCarcinoma, Renal CellUnited States, Italy, Brazil, Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czechia, France, Germany, Japan, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Spain, Switzerland, Turkey, United...