Induction Chemo-Nivo in Unresectable Stage III NSCLC

Sponsor

Ralph G Zinner (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06003075

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer, Nonsmall Cell Lung Cancer Stage III	Combination Product: Nivolumab and Chemotherapy Drug: Nivolumab Procedure: Post Induction Surgery Radiation: Post Induction XRT	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemoChemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Induction Platinum Doublet in Combination With Nivolumab Followed by Surgery or Concurrent Chemoradiation in Unresectable Stage IIIA-C Non-small Cell Lung Cancer (NSCLC)

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Aug 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
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 squamos; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamos) 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 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 squamos; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamos) 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 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.

Arm

Intervention/Treatment

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 squamos; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamos) 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

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

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

Radiation: Post Induction XRT

Outcome Measures

Primary Outcome Measures

Response rate after induction [9 weeks]
post induction radiographic response by cat scan

Secondary Outcome Measures

Change in Toxicity [through study completion, up to 18 months]
To assess safety, investigators will evaluate the rate of toxicity as defined by the Common Toxicity Criteria for Adverse Effects (CTCAE) scoring system.
Percent of participants receiving surgery [date of surgery, approximately 10 weeks]
Rate of converting non-surgical stage III(A-C) to surgically resectable disease
Pathologic complete response (pCR) [post surgery, approximately 10 weeks]
Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen
Major pathological response (MPR) [post surgery, approximately 10 weeks]
MPR rate, defined as number of participants with ≤ 10% residual tumor in lung and lymph nodes
Progression free survival [2 years]
PFS is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.
overall survival (OS) [2 years]
defined as the duration of time from start of treatment to time of death
Change in patient-reported Quality of Life as measured by FACT-TOI [through study completion, up to 18 months]
patient-reported Quality of Life as measured by FACT-TOI; defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Ralph G Zinner
Bristol-Myers Squibb

Investigators

Principal Investigator: Ralph Zinner, MD, University of Kentucky

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ralph G Zinner, Professor, University of Kentucky

ClinicalTrials.gov Identifier:

NCT06003075

Other Study ID Numbers:

85869

First Posted:

Aug 21, 2023

Last Update Posted:

Aug 21, 2023

Last Verified:

Aug 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ralph G Zinner, Professor, University of Kentucky

Nivolumab

unresectable

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Nivolumab

Study Results

No Results Posted as of Aug 21, 2023