Treatment with immunotherapy before and after surgery for the non small cell lung cancer

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; on small cell lung cáncer limited stage IIIA

• Registration Number: EUCTR2016-003732-20-ES
• Lead Sponsor: Grupo Español de Cáncer de Pulmón

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-17
• Last Update Posted: 31 January 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.The subjects eligible for the study are those with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) and previously untreated

2.Tumor should be considered resectable before study entry by a multidisciplinary team

3.Performance Status of 0 or 1 if using ECOG/Zubrod

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
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.The patients need to have a forced expiratory volume (FEV1) = 1.2 liters
ix.INR/APTT within normal limits

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

Age and Reproductive Status

6.Patients aged > 18 years

7.Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
8.Women must not be breastfeeding
9.Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 46
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

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. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.

3.Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

4.Patients with a history of interstitial lung disease cannot be included if they have sympthomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.

5.Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy

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 complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.

7.Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information

8.Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways

9.Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
10.Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
11.Patients with history of allergy to study drug components excipients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: -Assess the toxicity profile of the combination, the down-staging rate, complete resection rate, time to progression and overall survival at 3 years (follow up visits after adjuvant treatment, every 3 months for 3 years). Also, surgical outcome and operative and post-operative complications will be assessed.<br>-Perform correlatives studies with the objectives of exploring the expression of other biomarkers, such as PD-L1, in tumor tissue: at screening and after surgery (resected tumor sample), free DNA and circulating tumor cells in liquid biopsy<br>-To describe whether PD-L1 expression is a predictive biomarker for ORR<br>-To describe Progression Free Survival (PFS) in PD-L1+ (>=1%) population<br>-Report imaging response vs pathological response rate;Main Objective: Estimate progression-free survival (PFS) at 24 months from diagnosis;Primary end point(s): Progression-free survival (PFS) at 24 months from diagnosis;Timepoint(s) of evaluation of this end point: at 24 months from diagnosis