ACTIVE_NOT_RECRUITING

An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

Conditions

Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

An open label, randomized study of neoadjuvant nivolumab and chemotherapy, with or without sub-ablative stereotactic body radiation therapy, for resectable stage IIA to IIIB non-small cell lung cancer

Official Title

An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

Quick Facts

Study Start:2023-01-25

Study Completion:2030-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05500092

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patient has histologically or cytologically proven clinical stages IIA (tumors \> 4 cm), IIB, IIIA, and IIIB (T3 or T4, N2) NSCLC (AJCC version 8) and is considered eligible for surgical resection with curative intent. Patients with 2 primary non-small cell lung cancers are allowed. 2. Measurable disease, as defined by RECIST v1.1. 3. Parenchymal lung tumor deemed to be amenable to treatment with sub-ablative stereotactic body radiation therapy, as determined by a co-investigator from Radiation Oncology 4. Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) obtained from the subject prior to performing any protocol-related procedures. 5. Age \> 18 years at time of study entry 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate normal organ and marrow function as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3) * Platelet count ≥ 100 x 109/L (\>100,000 per mm3) * Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. * Aspartate aminotransferase (SGOT)/Alanine Aminotransferase (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN). * Serum creatinine clearance\>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (CL): 8. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: 9. Subject 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. 10. No prior therapy for their lung cancer.	1. Participation in another clinical study with an investigational product during the last 3 weeks. 2. Active other primary malignancy excepting: * Malignancy treated with curative intent and with no known active disease and of low potential risk for recurrence. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer, treated localized prostate cancer and ductal carcinoma-in situ. 3. Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 4. Patients with Grade ≥2 neuropathy. 5. Previous receipt of immunotherapy. 6. Active or prior documented autoimmune or inflammatory disorders that has required systemic treatment in the past year (including inflammatory bowel disease \[e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). No active diverticulitis within the previous 3 months. The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the study physician * Patients with celiac disease controlled by diet alone 7. History of allogeneic organ transplant. 8. History of hypersensitivity to nivolumab or any excipient. 9. Uncontrolled intercurrent illness that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 10. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), active hepatitis B (known positive Hepatitis B virus surface antigen (HBsAg) result), active hepatitis C. 11. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of nivolumab monotherapy. 12. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or evidence of active pneumonitis on screening chest CT scan. 13. Receipt of the last dose of therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) for an accepted other malignancy as defined in Section 3.3.2 within 30 days prior to the first dose of study drug for lung cancer.

Inclusion Criteria

Exclusion Criteria

1. Patient has histologically or cytologically proven clinical stages IIA (tumors \> 4 cm), IIB, IIIA, and IIIB (T3 or T4, N2) NSCLC (AJCC version 8) and is considered eligible for surgical resection with curative intent. Patients with 2 primary non-small cell lung cancers are allowed.
2. Measurable disease, as defined by RECIST v1.1.
3. Parenchymal lung tumor deemed to be amenable to treatment with sub-ablative stereotactic body radiation therapy, as determined by a co-investigator from Radiation Oncology
4. Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) obtained from the subject prior to performing any protocol-related procedures.
5. Age \> 18 years at time of study entry
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Adequate normal organ and marrow function as defined below:
* Hemoglobin ≥ 9.0 g/dL
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
* Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
* Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
* Aspartate aminotransferase (SGOT)/Alanine Aminotransferase (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).
* Serum creatinine clearance\>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (CL):
8. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
9. Subject 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.
10. No prior therapy for their lung cancer.

1. Participation in another clinical study with an investigational product during the last 3 weeks.
2. Active other primary malignancy excepting:
* Malignancy treated with curative intent and with no known active disease and of low potential risk for recurrence.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer, treated localized prostate cancer and ductal carcinoma-in situ.
3. Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
4. Patients with Grade ≥2 neuropathy.
5. Previous receipt of immunotherapy.
6. Active or prior documented autoimmune or inflammatory disorders that has required systemic treatment in the past year (including inflammatory bowel disease \[e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). No active diverticulitis within the previous 3 months. The following are exceptions to this criterion:
* Patients with vitiligo or alopecia
* Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
* Any chronic skin condition that does not require systemic therapy
* Patients without active disease in the last 5 years may be included but only after consultation with the study physician
* Patients with celiac disease controlled by diet alone
7. History of allogeneic organ transplant.
8. History of hypersensitivity to nivolumab or any excipient.
9. Uncontrolled intercurrent illness that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
10. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), active hepatitis B (known positive Hepatitis B virus surface antigen (HBsAg) result), active hepatitis C.
11. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of nivolumab monotherapy.
12. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or evidence of active pneumonitis on screening chest CT scan.
13. Receipt of the last dose of therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) for an accepted other malignancy as defined in Section 3.3.2 within 30 days prior to the first dose of study drug for lung cancer.

Contacts and Locations

Principal Investigator

Brendon Stiles, MD

PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Study Locations (Sites)

Washington University in St. Louis

St Louis, Missouri, 63130

United States

Montefiore Medical Center-Albert Einstein College of Medicine

The Bronx, New York, 10461

United States

White Plains Hospital (WPH)

White Plains, New York, 10601

United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033

United States

Collaborators and Investigators

Sponsor: Montefiore Medical Center

Brendon Stiles, MD, PRINCIPAL_INVESTIGATOR, Montefiore Medical Center

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 Registration Dates

Study Start Date2023-01-25

Study Completion Date2030-05

Study Record Updates

Study Start Date2023-01-25

Study Completion Date2030-05

Terms related to this study

Additional Relevant MeSH Terms

Resectable Stage IIA to IIIB Non-small Cell Lung Cancer