Study of chemotherapy and immunotherapy before and after surgery in patients with non-small cell lung cancer whose tumor is located in the upper part of the lungs

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion GECP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 May 2023 → ongoing

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

External identifiers

EU CT number

2024-512359-19-00

EudraCT number

2022-003717-11

ClinicalTrials.gov

NCT05684276

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Estimate progression-free survival (PFS) at 24 months from enrollment.
The PFS is defined as the time from enrollment to relapse, progression or death, whichever occurred first.

Secondary objectives 7

1. 1. Overall survival (OS) at 24 months
2. 2. Complete resection (R0) after induction treatment with chemotherapy plus nivolumab
3. 3. Objective treatment response rate (ORR), Disease control rate (DCR) and Duration of response (DOR)
4. 4. Pathological response: pCR, MPR, percentage of Residual Tumor Viable (RTV%) in the primary tumor
5. 5. Treatment safety and tolerability
6. 6.Study of the prognostic value of basal ctDNA (association of basal levels with PFS and OS) and to assess the minimal residual disease (MRD) in plasma samples
7. 7. To assess minimal residual disease (MRD) in the baseline tumor sample before treatment

Conditions and MedDRA coding

Resectable Non-small cell lung cancer Pancoast tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Previously untreated patients with histologically or cytologicallydocumented NSCLC diagnosed with Pancoast tumor according to 8th edition of the TNM (stages IIB, IIIA and T3N2 (IIIB) patients)
2. 2. PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before enrollment) to rule out the presence of distant disease. Also, a brain CT-SCAN or brain MRI will be done at baseline
3. 3. Positive mediastinal lymph nodes by PET-CT must be confirmed histologically. Mediastinal involvement may be considered without the need for histological confirmation when there is a mass of lymph nodes in which the margins cannot be distinguished
4. 4. Measurable or evaluable disease (according to RECIST 1.1 criteria)
5. 5. ECOG (Performance status) 0-2
6. 6. Patients with a life expectancy of at least more than 12 weeks
7. 7. Patients aged > 18 years and ≤ 75 years
8. 8. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to enrollment i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 ×109/L iii. Hemoglobin > 10.0 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 ≤ 2.5 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
9. 9. Correct lung function without bronchodilators, defined by forced expiratory volume in 1 second (FEV1) >40% of the predicted normal volume, and a pulmonary diffusing capacity for carbon monoxide (DLCO) >40% of the predicted normal value
10. 10. 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
11. 11. 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 enrollment.
12. 12. All sexually active men and women of childbearing potential must use an effective contracep-tive 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 following the last administration of trial drugs
13. 13. Patient capable of proper therapeutic compliance and accessible for correct follow-up.

Exclusion criteria 19

1. 1. Patients that receive previous treatment with antineoplastic drugs, chest radiotherapy, or previous surgery for lung cancer or for another reason
2. 2. Pleural or pericardial effusion: Both will be considered indicative of metastatic disease unless proven otherwise. Those that, even being cytologically negative for malignancy, are exudates, will also be excluded. Patients with pleural effusion not visible on chest X-ray or too small to perform diagnostic puncture safely may be included.
3. 3. Patients with a weight loss >10% in the 3 months prior to the study entry
4. 4. All patients carrying activating mutations in the TK domain of EGFR or any variety of altera-tions in the ALK gene or ROS1 mutations.
5. 5. Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hor-mone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
6. 6. Patients with symptomatic neuropathy > grade 1 according to the CTCAE v5.0 and that were not related to the tumor
7. 7. 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 replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
8. 8. 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.case of doubt please contact trial team.
9. 9. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy
10. 10. Patients with uncontrolled comorbidities that may affect the clinical trial compliance
11. 11. 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 5 years prior to study entry AND no additional therapy is required during the study period.
12. 12. Any medical, mental, neurological or psychological condition which in the opinion of the in-vestigator would not permit the patient to complete the study or understand the patient information sheet.
13. 13. Patients in any psychological, familiar, sociological or geographical situation that may hinder compliance with the study protocol and/or the follow up
14. 14. Patients who have had prior treatment with an anti-PD-1, anti-PDL1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
15. 15. 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
16. 16. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
17. 17. Patients with know hypersensitivity to drugs with a structure similar to the study drug and/or history of allergy to study drug components excipients
18. 18. Women who are pregnant or in the period of breastfeeding
19. 19. Sexually active men and women of childbearing potential who are not willing to use an ef-fective contraceptive method during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective is to estimate progression-free survival (PFS) at 24 months from enrollment. The PFS is defined as the time from enrollment to relapse, progression or death, whichever occurred first.

Secondary endpoints 7

1. 1. Overall survival rate (OS) at 24 months: Overall survival is defined as the time between the date of enrollment and the date of death. OS will be censored on the last date a participant was known to be alive
2. 2. Complete resection (R0) after induction treatment with chemotherapy plus nivolumab
3. 3. Objective treatment response rate (ORR), Disease control rate (DCR) and Duration of response (DOR). Systemic ORR, defined as a complete or partial response as determined by the investigator according to RECIST v1.1.
4. 4. Pathological response and percentage of Residual tumor viable (RTV%) in the primary tumor: pathological complete response (pCR) defined as the absence of residual tumor, Major pathological response rate (MPR), defined as number of randomized participants with <10% residual tumor
5. 5. Treatment safety and tolerability
6. 6.Study of the prognostic value of basal ctDNA (association of basal levels with PFS and OS) and to assess the minimal residual disease (MRD) in plasma samples
7. 7. To assess minimal residual disease (MRD) in the baseline tumor sample before treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Scientific contact point

Organisation

Fundacion GECP

Contact name

Mariano Provencio

Public contact point

Organisation

Fundacion GECP

Contact name

Maria Fernandez

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications