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

Primary Purpose

Non Small Cell Lung Cancer

Status
Active
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Nivolumab 360 mg
Paclitaxel 200mg/m2
Carboplatin AUC 6
Sponsored by
Spanish Lung Cancer Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Complejo hospitalario de la coruña
  • Hospital Reina Sofía
  • Hospital Insular de Gran Canaria
  • Hospital Puerta de Hierro
  • Clínica Universitaria de Navarra
  • Complejo Hospitalario de Vigo
  • Hospital de Cruces
  • Hospital General de Alicante
  • Hospital Universitari Quirón Dexeus
  • Hospital Universitari Vall Hebrón
  • Hospital Clínic de Barcelona
  • Hospital de La Santa Creu I Sant Pau
  • H. Duran i Reynals-ICO
  • H. de la Princesa
  • Hospital Clínico San Carlos
  • Hospital Fundación Jiménez Díaz
  • H. La Paz
  • Hospital Son Espases
  • Hospital Clinico de Salamanca
  • Hospital Virgen de La Macrena
  • Hospital Virgen Del Rocío
  • Hospital Clínico Universitario de Valencia
  • H. Gen. Univ. Valencia
  • Hospital La Fe

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival
Time when the patient is still alive
Toxicity profile
Toxicities caused by the drug during the study

Full Information

First Posted
March 10, 2017
Last Updated
January 9, 2023
Sponsor
Spanish Lung Cancer Group
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1. Study Identification

Unique Protocol Identification Number
NCT03081689
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 15, 2017 (Actual)
Primary Completion Date
September 15, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spanish Lung Cancer Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Nivolumab 360 mg
Other Intervention Name(s)
OPDIVO
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Paclitaxel 200mg/m2
Other Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel 200mg/m2 IV Q3W
Intervention Type
Drug
Intervention Name(s)
Carboplatin AUC 6
Other Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin AUC 6 IV Q3W
Primary Outcome Measure Information:
Title
Progression free survival
Description
The progression free survival is the time until the patients disease progresses
Time Frame
at 24 months from the first dose of neadjuvant treatment
Secondary Outcome Measure Information:
Title
Overall survival
Description
Time when the patient is still alive
Time Frame
at 3 years from the first dose of neoadjuvant treatment
Title
Toxicity profile
Description
Toxicities caused by the drug during the study
Time Frame
from the first dose of neoadjuvant treatment until 90 days after the last dose of adjuvant treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mariano Provencio, MD
Organizational Affiliation
spanish Lun Cancer Group
Official's Role
Study Chair
Facility Information:
Facility Name
Complejo hospitalario de la coruña
City
La Coruña
State/Province
Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Reina Sofía
City
Cordoba
State/Province
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Insular de Gran Canaria
City
Las Palmas De Gran Canaria
State/Province
Gran Canaria
ZIP/Postal Code
35016
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Clínica Universitaria de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Complejo Hospitalario de Vigo
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36212
Country
Spain
Facility Name
Hospital de Cruces
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital General de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital Universitari Quirón Dexeus
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
Hospital Universitari Vall Hebrón
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital de La Santa Creu I Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
H. Duran i Reynals-ICO
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
H. de la Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Fundación Jiménez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
H. La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Son Espases
City
Palma de Mallorca
ZIP/Postal Code
07010
Country
Spain
Facility Name
Hospital Clinico de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Virgen de La Macrena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Virgen Del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
H. Gen. Univ. Valencia
City
Valencia
Country
Spain
Facility Name
Hospital La Fe
City
Valencia
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35576508
Citation
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.
Results Reference
derived
PubMed Identifier
34446577
Citation
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.
Results Reference
derived
PubMed Identifier
34376534
Citation
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.
Results Reference
derived
PubMed Identifier
34323406
Citation
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.
Results Reference
derived
PubMed Identifier
32979984
Citation
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.
Results Reference
derived
Links:
URL
http://www.gecp.org
Description
Web page of the sponsor where users can find more information about SLCG studies

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

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