Study of Atezolizumab plus chemotherapy plus chemo-radiotherapy and Atezolizumab maintenance therapy in non-resectable non-small cell lung cancer patients

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

16 Jun 2021 → 31 Jul 2025

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

External identifiers

EU CT number

2024-514803-33-00

EudraCT number

2020-004459-33

ClinicalTrials.gov

NCT04776447

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival (PFS) at 12 months according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. PFS is defined as the time from inclusion until objective tumor progression or death.

Secondary objectives 5

1. 1. To evaluate the ORR of the treatment as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1.
2. 2. To evaluate the PFS rate at 24 months of the treatment.
3. 3. To evaluate the Overall survival (OS) rate at 12 and 24 months of the treatment.
4. 4. To evaluate the sites of first failure
5. 5. To evaluate the safety and tolerability of Atezolizumab in combination with chemotherapy and Atezolizumab as maintenance treatment.

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Male or female, aged ≥ 18 years old and ≤ 80 years
2. 2. ECOG performance status of 0 or 1.
3. 3. Histologically or cytologically confirmed, non-resectable Stage IIIA-IIIB-IIIC (IIIC: only candidates for radical CT-RDT). NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
4. 4. PET-CT and brain CT or MRI at baseline to confirm the absence of distant disease
5. 5. Mediastinal involvement could be considered without histological confirmation when no margin can be distinguished in the lymph node mass.
6. 6. No prior treatment with anti-neoplasic drugs or thoracic radiotherapy for non-resectable Stage IIIA-IIIB-IIIC NSCLC.
7. 7. Presence of at least one measurable disease by CT-SCAN, as defined by RECIST v1.1.
8. 8. Adequate hematologic and organ function defined by laboratory results obtained within 14 days prior to enrollment
9. 9. 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.
10. 10. Adequate lung function: Forced Espiratoy Volumen in 1 second (FEV1) >50% of normal volume and Difusion Capacity of the Lungs for Carbon Monoxide (DLCO) >40% of normal value
11. 11. No more than 35% of the total volume of the two lungs should receive more than 20 Gy (V20) or no more than 7cm maximum diameter
12. 12. For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of trial treatment.
13. 13. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate [< 1% per year] when used consistently and correctly, and to continue its use for 6 months after the last dose of trial treatment. Male patients should not donate sperm during this study and for at least 6 months after the last dose of trial treatment.
14. 14. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs. The same rules are valid for male patients involved in this clinical study if they have a partner of childbirth potential. Male patients must always use a condom.
15. 15. Women who are not postmenopausal (≥ 12 months of non−therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 8 days prior to initiation of study drug.

Exclusion criteria 24

1. 1. Patients with known sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene, ALK fusion oncogene
2. 2. Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
3. 3. Weight loss >10% within the previous 3 months.
4. 4. Malignant pleural effusion or pericardial effusion: both will be considered as suggestive of metastasic disease. Also excluded those with negative cytology but being exudates. Patients with non-visible by thoracic X-Ray pleural effusion or too small to be safely punctioned could be included.
5. 5. Malignancies other than NSCLC within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 3-year OS > 90%) treated with expected curative outcome
6. 6. Women who are pregnant, lactating, or intending to become pregnant during the study.
7. 7. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab formulation.
8. 8. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. "
9. 9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
10. 10. Positive test for HIV. All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical study.
11. 11. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
12. 12. Active tuberculosis.
13. 13. Symptomatic neuropathy (sensory) grade > 1 according to the NCI Common Toxicity Criteria for Adverse Events v5.0
14. 14. Severe infections within 4 weeks prior to be included in the study, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
15. 15. Received therapeutic oral or IV antibiotics within 2 weeks prior to be included in the study.
16. 16. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate."
17. 17. Patients with a superior vena cava syndrome.
18. 18. Major surgical procedure other than for diagnosis within 28 days prior to inclusion or anticipation of need for a major surgical procedure during the course of the study.
19. 19. Prior allogeneic bone marrow transplantation or solid organ transplant.
20. 20. Administration of a live, attenuated vaccine within 4 weeks before inclusion or anticipation that such a live attenuated vaccine will be required during the study.
21. 21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
22. 22. Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures.
23. 23. Treatment with any other investigational agent with therapeutic intent within 28 days prior to initiation of study treatment.
24. 24. Treatment with systemic immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival (PFS) at 12 months according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Secondary endpoints 5

1. "1. To evaluate the ORR of the treatment as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1."
2. 2. To evaluate the PFS rate at 24 months of the treatment.
3. 3. To evaluate the Overall survival (OS) rate at 12 and 24 months of the treatment.
4. 4. To evaluate the sites of first failure
5. 5. To evaluate the safety and tolerability of Atezolizumab in combination with chemotherapy and Atezolizumab as maintenance 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 Fernández

Locations

1 EU/EEA country · 22 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

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

Application history

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