Study of Nivolumab and Ipilimumab plus chemotherapy as a treatment for patients with stage IV lung cancer with brain metastases.

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

18 Nov 2021 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundacion GECP

External identifiers

EU CT number

2024-513866-20-00

EudraCT number

2021-000425-27

ClinicalTrials.gov

NCT05012254

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective of this trial is to determine the rate of intracranial clinical benefit, defined as the percentage of patients who had lack of radiological or clinical progression for at least 6 months according to RANO-BM assessment criteria

Secondary objectives 5

1. 1. To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
2. 2. To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of the investigator assessed bicompartimental PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria
3. 3. To evaluate the safety of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases.
4. 4. Overall survival (OS) at 12, 18 and 24 defined as the time from enrollment to death from any cause at this landmark timepoints
5. 5. To determine the quality of life (QoL)

Conditions and MedDRA coding

Non-small cell lung cancer with brain metastasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. COHORT A - Patients with histologically or cytologically confirmed stage IV NSCLC who did not receive any prior systemic therapy for advanced disease and have synchronous untreated brain metastases which does not cause neurologic symptoms and does not require systemic corticosteroid treatment within 10 days before initiating study treatment (controlled seizures with antiepileptic drugs should be allowed).
2. 2. COHORT B: -Patients with histologically or cytolotically confirmed stage IV NSCLC who did not receive any prior systemic therapy for advanced disease and have synchronous brain metastasis causing neurologic signs and symptoms controlled with medium-low doses of corticosteroids (≤ 25mg/d of prednisone or ≤ 4mg/d of dexamethasone) but have good performance status (ECOG PS0-1). -At least one untreated brain lesion in patients who already received focal radiotherapy (stereotactic focal radiotherapy) of prior brain lesions are eligible if novel brain lesions appear which are measurable and not suitable for focal radiotherapy
3. 3. Patients with early or locally advanced NSCLC who have recurred after 6 months of completing adjuvant or neoadjuvant chemotherapy and have brain metastases are also eligible
4. 4. ECOG performance status 0-1
5. 5. Patients aged ≥ 18 years
6. 6. Systemic measurable disease by computed tomography (CT) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria and brain measurable disease by magnetic resonance imaging (MRI) per RANO-BM criteria
7. 7. Availability of a formalin-fixed paraffin-embedded block containing tumor tissue or 10 unstained slides. Archival tumor tissue can be sent if it was obtained less than 12 months ago.
8. 8. Correct hematological, hepatic and renal function
9. 9. Patient consent must be obtained in the appropriate manner as established in the applicable local and regulatory requirements
10. 10. Patients must be accessible for treatment and follow-up
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 3 days before enrollment.
12. 12. All sexually active men and women of childbearing potential must use a highly effective contraceptive method (<1% failure rate) during the study treatment and for a period of at least 5 months for females and 7 months for males following the last administration of trial drugs

Exclusion criteria 19

1. 1. Patients with a history of other malignant diseases within the past 3 years, with the exception of the following: properly treated non-melanotic skin cancer; cancer in situ treated with curative intent; nonmuscularis propia invasive carcinoma of the bladder; or other malignancies treated with curative intent and without signs of disease for a period of > 3 years after the end of the treatment and which, in the opinion of the physician in charge of their treatment, do not present a substantial risk of relapse of the previous malignant disease.
2. 2. Patients harboring epidermal growth factor receptor (EGFR) mutations or anaplastic lym-phoma kinase (ALK) and ROS Proto-Oncogene 1 (ROS1) rearrangements
3. 3. Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
4. 4. Patients that received live attenuated vaccines within 30 days prior to enrollment
5. 5. Leptomeningeal carcinomatosis or metastases in the brain stem, mid-brain, pons, medulla or causing obstructive hydrocephalus
6. 6. Brain metastasis amenable to surgical treatment or radiosurgery
7. 7. Prior surgical resection of brain or spinal lesions in the prior 28 days
8. 8. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months be-fore enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy
9. 9. History of a primary immunodeficiency, history of organ allogeneic transplantation, use of immunosuppressive drugs within 28 days before enrollment or previous history of toxicity of severe immune mechanism (grade 3 or 4) with other immunological treatments
10. 10. Patients with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to be enrolled
11. 11. Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol
12. 12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of radiation pneumonitis put of the radiation field on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
13. 13. Significant comorbidities that preclude the administration of chemotherapy according to the investigator’s criteria
14. 14. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative)
15. 15. Previous treatment with immune checkpoint inhibitors
16. 16. Patients who have suffered untreated and / or uncontrolled cardiovascular disorders and / or who have symptomatic cardiac dysfunction
17. 17. Pregnant or breastfeeding women
18. 18. History of allergy or hypersensitivity to any of the study drug components
19. 19. Patients with a condition other than brain metastases requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective of this trial is to determine the rate of intracranial clinical benefit, defined as the percentage of patients who had lack of radiological or clinical progression for at least 6 months according to RANO-BM assessment criteria.

Secondary endpoints 5

1. 1. To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
2. 2, To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of the investigator assessed bicompartimental PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria
3. 3, To evaluate the safety of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases.
4. 4, Overall survival (OS) at 12, 18 and 24 defined as the time from enrollment to death from any cause at this landmark timepoints
5. 5, To determine the quality of life (QoL)

Investigational products

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

Test 2

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 · 18 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

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