UK Center for Clinical and Translational Science

Induction Chemo-Nivo in Unresectable Stage III NSCLC

Purpose

The purpose of this study is to determine the response rate, safety, and effectiveness of a combination therapy in patients with lung cancer.

Conditions

Lung Cancer, Nonsmall Cell
Lung Cancer Stage III

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Squamous and non-squamous non-small cell lung cancer that is at baseline, unresectable stage IIIA-IIIC (8th edition AJCC) and not previously treated - PD-L1 level needs to be measured with values 0-100% eligible - EGFR/ALK/ROS1 Wild Type or unknown genetic alterations in these genes - ECOG Performance Status ≤ 1 - Adequate organ and marrow function - Adequate pulmonary reserve (e.g., FVC, FEV1, TLC, FRC, and DLCO) capable of tolerating the proposed lung resection - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen - Clinical risk assessment of cardiac function using the New York Heart Association Functional Classification class 2B or better - Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment - Any prior radiotherapy to the lung - Any prior treatment for NSCLC - Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways - Any history of a severe hypersensitivity reaction to any monoclonal antibody - Any history of allergy to the study drug components - primary tumors involving the esophagus - pancoast tumors - Patients cannot have primary tumors which would remain unresectable - History of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab or other agents used in study - Any active or history of autoimmune disease (including any history of inflammatory bowel disease), or history of syndrome that required systemic steroids or immunosuppressive medications - Ongoing requirement for systemic corticosteroids greater than the equivalent of prednisone 10mg - previous malignancies - history of interstitial lung disease - Patients requiring continuous supplemental oxygen - Use of any live vaccines against infectious diseases (e.g., influenza, varicella. etc.) within 4 weeks (28 days) of initiation of study therapy - Active systemic infection requiring therapy - Patients with uncontrolled intercurrent illness - Patients with psychiatric illness/social situations that would limit compliance with study requirements - Pregnant or lactating women

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Combination Chemotherapy and Nivolumab and Surgery	Patients with lung cancer receiving combination therapy with surgery	Combination Product: Nivolumab and Chemotherapy 3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks Drug: Nivolumab Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation Other names: NIVO Procedure: Post Induction Surgery Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by surgery in patients whose tumors were unresectable stage IIIA-C at baseline on the basis of lymphadenopathy and are determined to be resectable after responding to induction chemotherapy-nivolumab. The participants have an option for post op XRT, then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles Radiation: Post Induction XRT Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.
Experimental Combination Chemotherapy and Nivolumab and Radiation	Patients with lung cancer receiving combination therapy with radiation	Combination Product: Nivolumab and Chemotherapy 3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks Drug: Nivolumab Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation Other names: NIVO Radiation: Post Induction XRT Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40506

Contact:
Yvonne Taul, RN

More Details

NCT ID: NCT06003075
Status: Recruiting
Sponsor: Ralph G Zinner

Study Contact

Yvonne Taul, RN
859-323-2354
yvonne.taul@uky.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.