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

NCT03081689 | Completed Phase 2 Results DMC

• 1 other identifier: GECP 16/03_NADIM
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 24

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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The progression free survival is the percentage of the patients without disease progression

  at 24 months from the first dose of neoadjuvant treatment

Secondary Outcomes (1)

• Overall Survival

  at 3 years from the first dose of neoadjuvant treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

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

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

Interventions

Nivolumab 360 mg DRUG

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

Also known as: OPDIVO

Arm 1

Paclitaxel 200mg/m2 DRUG

Paclitaxel 200mg/m2 IV Q3W

Also known as: Paclitaxel

Arm 1

Carboplatin AUC 6 DRUG

Carboplatin AUC 6 IV Q3W

Also known as: Carboplatin

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Tumor should be considered resectable before study entry
• Performance Status of 0 or 1
• \. 72 x serum creatinine in mg/dL
• b. Male CrCl = (140 - age in years) x weight in kg x 1.00
• 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
• \. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters
• \. 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.
• \. Patients aged \> 18 years
• \. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
• \. Women must not be breastfeeding
• \. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

You may not qualify if:

• All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.
• Patients with active, known or suspected autoimmune disease.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• Patients with a history of interstitial lung disease cannot be included if they have sympthomatic ILD (Grade 3-4)
• Patients with other active malignancy requiring concurrent intervention
• 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
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study
• Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody,
• Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody)
• Patients with known history of testing positive for human immunodeficiency virus (HIV)
• Patients with history of allergy to study drug components excipients

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (24)

Complejo hospitalario de la coruña

A Coruña, Coruña, 15006, Spain

Location

Hospital Reina Sofía

Córdoba, Córdoba, 14004, Spain

Location

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

Hospital Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Complejo Hospitalario de Vigo

Vigo, Pontevedra, 36212, Spain

Location

Hospital de Cruces

Bilbao, Vizcaya, 48903, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital Universitari Quirón Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitari Vall Hebrón

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

H. Duran i Reynals-ICO

Barcelona, 08907, Spain

Location

H. de la Princesa

Madrid, 28006, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

H. La Paz

Madrid, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07010, Spain

Location

Hospital Clinico de Salamanca

Salamanca, 37007, Spain

Location

Hospital Virgen de La Macrena

Seville, 41009, Spain

Location

Hospital Virgen Del Rocío

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

H. Gen. Univ. Valencia

Valencia, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Related Publications (6)

• 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.

  PMID: 35576508 RESULT

• 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.

  PMID: 32979984 RESULT

• Provencio M, Nadal E, Insa A, Garcia Campelo R, Casal J, Domine M, Massuti B, Majem M, Rodriguez-Abreu D, Martinez-Marti A, de Castro J, Gomez de Antonio D, Macia I, Figueroa S, Fernandez Vago L, Calvo V, Palmero R, Sierra-Rodero B, Martinez-Toledo C, Molina-Alejandre M, Serna-Blasco R, Romero A, Cruz-Bermudez A. Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2024 Nov;25(11):1453-1464. doi: 10.1016/S1470-2045(24)00498-4. Epub 2024 Oct 14.

  PMID: 39419061 DERIVED

• 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.

  PMID: 34446577 DERIVED

• 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.

  PMID: 34376534 DERIVED

• 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.

  PMID: 34323406 DERIVED

Related Links

• Web page of the sponsor where users can find more information about SLCG studies

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34934302006

Study Officials

• Mariano Provencio, MD

  spanish Lun Cancer Group

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 16, 2017
• Study Start: April 15, 2017
• Primary Completion: September 15, 2023
• Study Completion: October 18, 2023
• Last Updated: December 4, 2024
• Results First Posted: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (24)