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

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03081689
• Other study ID #: GECP 16/03_NADIM
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2017
• Est. completion date: October 18, 2023

Study information

• Verified date: January 2024
• Source: Spanish Lung Cancer Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 18, 2023
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• 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
• Paclitaxel 200mg/m2
Paclitaxel 200mg/m2 IV Q3W
• Carboplatin AUC 6
Carboplatin AUC 6 IV Q3W

Locations

Country	Name	City	State
Spain	Hospital General de Alicante	Alicante
Spain	H. Duran i Reynals-ICO	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitari Quirón Dexeus	Barcelona
Spain	Hospital Universitari Vall Hebrón	Barcelona
Spain	Hospital de Cruces	Bilbao	Vizcaya
Spain	Hospital Reina Sofía	Cordoba	Córdoba
Spain	Complejo hospitalario de la coruña	La Coruña	Coruña
Spain	Hospital Insular de Gran Canaria	Las Palmas De Gran Canaria	Gran Canaria
Spain	H. de la Princesa	Madrid
Spain	H. La Paz	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Fundación Jiménez Díaz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Clínica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Clinico de Salamanca	Salamanca
Spain	Hospital Virgen de La Macrena	Sevilla
Spain	Hospital Virgen Del Rocío	Sevilla
Spain	H. Gen. Univ. Valencia	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital La Fe	Valencia
Spain	Complejo Hospitalario de Vigo	Vigo	Pontevedra

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Lung Cancer Group

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	The progression free survival is the time until the patients disease progresses	at 24 months from the first dose of neadjuvant treatment
Secondary	Overall survival	Time when the patient is still alive	at 3 years from the first dose of neoadjuvant treatment
Secondary	Toxicity profile	Toxicities caused by the drug during the study	from the first dose of neoadjuvant treatment until 90 days after the last dose of adjuvant treatment

External Links

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