Neo-Adjuvant Immunotherapy With Nivolumab for Non Small Cell Lung Cancer Patients

• ClinicalTrials.gov Identifier: NCT03081689
• Recruitment Status: Completed
• First Posted: March 16, 2017
• Last Update Posted: January 18, 2024
• Sponsor: Spanish Lung Cancer Group
• Information provided by (Responsible Party): Spanish Lung Cancer Group

Tracking Information

• First Submitted Date: March 10, 2017
• First Posted Date: March 16, 2017
• Last Update Posted Date: January 18, 2024
• Actual Study Start Date: April 15, 2017
• Actual Primary Completion Date: September 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2017)

Progression free survival [ Time Frame: at 24 months from the first dose of neadjuvant treatment ]

The progression free survival is the time until the patients disease progresses

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 10, 2017)

• Overall survival [ Time Frame: at 3 years from the first dose of neoadjuvant treatment ]
  Time when the patient is still alive
• Toxicity profile [ Time Frame: from the first dose of neoadjuvant treatment until 90 days after the last dose of adjuvant treatment ]
  Toxicities caused by the drug during the study

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neo-Adjuvant Immunotherapy With Nivolumab for Non Small Cell Lung Cancer Patients
• Official Title: Neo - Adjuvant Chemo / Immunotherapy for the Treatment of Resectable Stage IIIA Non Small Cell Lung Cancer (NSCLC): A Phase II Multicenter Exploratory Study
• Brief Summary: Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months.

Detailed Description

Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months.

Three cycles of neoadjuvant chemotherapy in combination with nivolumab will be administered.

After completion of neoadjuvant therapy (3 cycles) and before surgery, a tumor assessment will be done. Patients have to leave the study if there is evidence of progression. Patients with in-stable disease or partial response may be considered for surgery.

The report imaging response vs pathological response rate will be evaluated.

Patients eligible for the trial are those with a histological diagnosis or cytologically proven operable and resectable non-small-cell lung cancer. The total number of patients to be included will be 46 from 23 participating sites in Spain.

Accrual period of 1.5 years or until the inclusion of the last patient necessary to achieve the sample set in the protocol of 46 patients. After that all patients will be treated for 1 year with adjuvant immunotherapy and they will be followed during 3 years after adjuvant treatment.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: Nivolumab 360 mg
  Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months
  Other Name: OPDIVO
• Drug: Paclitaxel 200mg/m2
  Paclitaxel 200mg/m2 IV Q3W
  Other Name: Paclitaxel
• Drug: Carboplatin AUC 6
  Carboplatin AUC 6 IV Q3W
  Other Name: Carboplatin

Study Arms

Experimental: Arm 1

Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months

Interventions:

• Drug: Nivolumab 360 mg
• Drug: Paclitaxel 200mg/m2
• Drug: Carboplatin AUC 6

Publications *

• Provencio M, Serna-Blasco R, Nadal E, Insa A, Garcia-Campelo MR, Casal Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Calvo V, Martin-Lopez J, Garcia-Garcia F, Casarrubios M, Franco F, Sanchez-Herrero E, Massuti B, Cruz-Bermudez A, Romero A. Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial). J Clin Oncol. 2022 Sep 1;40(25):2924-2933. doi: 10.1200/JCO.21.02660. Epub 2022 May 16. Erratum In: J Clin Oncol. 2022 Nov 10;40(32):3785.
• Sierra-Rodero B, Cruz-Bermudez A, Nadal E, Garitaonaindia Y, Insa A, Mosquera J, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Laza-Briviesca R, Casarrubios M, Garcia-Grande A, Romero A, Franco F, Provencio M. Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial. J Immunother Cancer. 2021 Aug;9(8):e002804. doi: 10.1136/jitc-2021-002804.
• Casarrubios M, Cruz-Bermudez A, Nadal E, Insa A, Garcia Campelo MDR, Lazaro M, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, de Castro-Carpeno J, Cobo M, Lopez-Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Barquin M, Laza-Briviesca R, Sierra-Rodero B, Parra ER, Sanchez-Espiridion B, Rocha P, Kadara H, Wistuba II, Romero A, Calvo V, Provencio M. Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy. Clin Cancer Res. 2021 Nov 1;27(21):5878-5890. doi: 10.1158/1078-0432.CCR-21-1200. Epub 2021 Aug 10.
• Laza-Briviesca R, Cruz-Bermudez A, Nadal E, Insa A, Garcia-Campelo MDR, Huidobro G, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Casarrubios M, Sierra-Rodero B, Tarin C, Garcia-Grande A, Haymaker C, Wistuba II, Romero A, Franco F, Provencio M. Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial. Clin Transl Med. 2021 Jul;11(7):e491. doi: 10.1002/ctm2.491.
• Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 10, 2017): 46
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 18, 2023
• Actual Primary Completion Date: September 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The subjects eligible for the study are those with histologically- or cytologically- documented NSCLC who present stage IIIA disease. Locally advanced patients who present stage IIIA by the previous version can be included if are considered potencially resectable. In case of N2 disease suspicion, pathological assessment by EBUS, mediastinoscopy or thoracotomy has to be carried out for N2 confirmation.
2. Tumor should be considered resectable before study entry
3. Performance Status of 0 or 1
4. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration/inclusion i. WBC ≥ 2000/μL ii. Neutrophils ≥ 1500/μL iii. Platelets ≥ 100 x103/μL iv. Hemoglobin > 9.0 g/dL v. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): a. Female CrCl = (140 - age in years) x weight in kg x 0.85

1. 72 x serum creatinine in mg/dL

b. Male CrCl = (140 - age in years) x weight in kg x 1.00

1. 72 x serum creatinine in mg/dL vi. AST/ALT ≤ 3 x ULN vii. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) viii. INR/APTT within normal limits

   5. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters

   6. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and nacional guidelines, including the Declaration of Helsinki prior to any trial-related intervention.

   7. Patients aged > 18 years

   8. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.

   9. Women must not be breastfeeding

   10. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

   Exclusion Criteria:

   1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.
   2. Patients with active, known or suspected autoimmune disease.
   3. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
   4. Patients with a history of interstitial lung disease cannot be included if they have sympthomatic ILD (Grade 3-4)
   5. Patients with other active malignancy requiring concurrent intervention
   6. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a
   7. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study
   8. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody,
   9. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody)
   10. Patients with known history of testing positive for human immunodeficiency virus (HIV)
   11. Patients with history of allergy to study drug components excipients

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT03081689
• Other Study ID Numbers: GECP 16/03_NADIM
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Spanish Lung Cancer Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Spanish Lung Cancer Group
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Mariano Provencio, MD; spanish Lun Cancer Group

• PRS Account: Spanish Lung Cancer Group
• Verification Date: January 2024