Study of chemotherapy and immunotherapy for patients with lung cancer bounded in the thorax and potentially resectable

Phase 1

Conditions: on-small cell lung cancer
MedDRA version: 20.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-004515-45-ES

Lead Sponsor: Fundación GECP

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 90

Inclusion Criteria

1.Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to 8th version of the Interna-tional Association for the Study of Lung Cancer Staging Manual in Thoracic Oncol-ogy) and also, potentially resectable locally advanced NSCLC patients’ stage IIIB with T3N2 disease according to 8th edition can be included.
-PET/CT including IV contrast (CT of diagnostic quality) will be per-formed at baseline
2.Tumor should be considered resectable before study entry by a multidisciplinary team

3.ECOG (Performance status) 0-1

4.Screening laboratory values must meet the following criteria and should be ob-tained within 14 days prior to registration/inclusion
i.Neutrophils = 1500×109/L
ii.Platelets = 100 x×109/L
iii.Hemoglobin > 9.0 g/dL
iv.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/
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
v.AST/ALT = 3 x ULN
vi.Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
vii.The patients need to have a forced expiratory volume (FEV1) = 1.2 liters or >40% predicted value
viii.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

6.Patients aged > 18 years

7.Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before beginning of chemotherapy.

8.All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months follow-ing the last administration of trial drugs

9.Patient capable of proper therapeutic compliance and accessible for correct fol-low-up

10.Measurable or evaluable disease (according to RECIST 1.1 criteria)
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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

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 viti-ligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thy-roiditis only requiring hormone replacement or unexpected conditions of recur-rence 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 enrollment. Inhaled or topical steroids, and adrenal replace-ment 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 inves-tigator would not permit the patient to complete the study or understand the pa-tient 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 hep-atitis 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
12.Women who are pregnant or in the period of breastfeeding
13.Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is pathological Complete Response (pCR) defined as the absence of residual tumor in lung and lymph nodes comparing patients treated with chemo-inmunotherapy versus chemotherapy alone;<br> Secondary Objective: - Overall survival<br> - Progression-free survival<br> - Major pathological response rate<br> - Downstaging<br> - Portion of delayed/canceled surgeries, length of hospital stays, surgical ap-proach, incidence of AE/SAE related to surgery<br> - Mortality at 90 days after surgery<br> - Safety and tolerability: Adverse events graded according to CTCAE v5.0<br> - Biomarker endpoints<br> ;Primary end point(s): pathological Complete Response (pCR);Timepoint(s) of evaluation of this end point: 6 months after start the treatment

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - Overall survival<br> - Progression-free survival<br> - Major pathological response rate<br> - Downstaging<br> - Portion of delayed/canceled surgeries, length of hospital stays, surgical ap-proach, incidence of AE/SAE related to surgery<br> - Mortality at 90 days<br> - Safety and tolerability`<br> - Biomarker endpoints<br> ;Timepoint(s) of evaluation of this end point: at the end of the follow up

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