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Non Small Cell Lung CancerPhase 2NIVIPI-BrainNCT05012254

Nivolumab and Ipilimumab Plus Chemotherapy for Patients With Stage IV Lung Cancer With Brain Metastases

A Phase 2 study testing Ipilimumab, Nivolumab and Carboplatin in people with Non Small Cell Lung Cancer and Brain Metastases, Adult, run by Fundación GECP at 18 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is an open-label, non-randomised, phase II, multicenter clinical trial. 71 stage IV or recurrent, non-small cell lung cancer patients with synchronous brain metastases will be enrolled in this trial to evaluate the efficacy of Nivolumab plus Ipilimumab plus two cycles of platinum-based chemotherapy as first line… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ipilimumab, Nivolumab and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
18 sitesSpain
Study dates
18 Nov 2021to 15 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • COHORT B Patients with histologically or cytologically 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. 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
  • ECOG performance status 0-1
  • Patients aged ≥ 18 years
  • 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.
  • 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.
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  • Correct hematological, hepatic and renal function. i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 ×109/L iii. Hemoglobin ≥ 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 45 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. Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 x ULN) vii. PT/APTT ≤ 1.5 × upper limit of normal (ULN). This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
  • Patient consent must be obtained in the appropriate manner as established in the applicable local and regulatory requirements
  • Patients must be accessible for treatment and follow-up
  • 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 randomization.
  • 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.

Who cannot join

  • 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
  • nonmuscular propria 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.
  • Patients harboring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) and ROS Proto-Oncogene 1 (ROS1) rearrangements sensitive to available targeted inhibitor therapy
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  • Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
  • Patients that received live attenuated vaccines within 30 days prior to randomization
  • Leptomeningeal carcinomatosis or metastases in the brain stem, mid-brain, pons, medulla or causing obstructive hydrocephalus
  • Single exclusive brain metastasis amenable to surgical treatment or radiosurgery
  • Prior surgical resection of brain or spinal lesions in the prior 28 days
  • Patients who have received prior neoadjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months before enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy
  • History of a primary immunodeficiency, history of organ allogeneic transplantation, use of immunosuppressive drugs within 28 days before randomization or previous history of toxicity of severe immune mechanism (grade 3 or 4) with other immunological treatments
  • 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
  • Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol
  • 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.
  • Significant comorbidities that preclude the administration of chemotherapy according to the investigator's criteria
  • 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)
  • Previous treatment with immune checkpoint inhibitors
  • Patients who have suffered untreated and / or uncontrolled cardiovascular disorders and / or who have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction in the previous year or ventricular cardiac arrhythmias that require medication, history of atrioventricular conduction of second or third degree)
  • Pregnant or breastfeeding women
  • History of allergy or hypersensitivity to any of the study drug components
  • 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 randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

Spain18 sites

  • Hospitalario Universitario A Coruña

    A Coruña, La Coruña, 15006

  • ICO Badalona, Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitari Vall d' Hebron

    Barcelona, Barcelona, 08035

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Barcelona, 08041

  • Hospital Provincial de Castellón

    Castellon, Castellon, 12002

  • Hospital Universitario de Jaén

    Jaén, Jaén, 23007

  • ICO Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitario Insular de Gran canaria

    Las Palmas de Gran Canaria, Gran Canaria, 35016

  • Hospital Universitario de León

    León, León, 24071

  • Hospital Universitario Lucus Augusti

    Lugo, Lugo, 27003

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, Madrid, 28040

  • Hospital 12 De Octubre

    Madrid, Madrid, 28041

  • Hospital Universitario Puerta de Hierro

    Majadahonda, Madrid, 28222

  • Hospital Universitario Regional de Málaga

    Málaga, Málaga, 29010

  • Hospital Universitari Son Llatzer

    Palma de Mallorca, Palma de Mallorca, 07198

  • Hospital General Universitario de Valencia

    Valencia, Valencia, 46014

  • Hospital Universitario La Fe

    Valencia, Valencia, 46026

  • Hospital Clínico Universitario de Valladolid

    Valladolid, Valladolid, 47003

Other trials in Spain

About this study

Official title: Nivolumab Plus Ipilimumab Plus Two Cycles of Platinum-based Chemotherapy as First Line Treatment for Stage IV/Recurrent Non-small Cell Lung Cancer (NSCLC) Patients With Synchronous Brain Metastases

This is an open-label, non-randomised, phase II, multicenter clinical trial.

71 stage IV or recurrent, non-small cell lung cancer patients with synchronous brain metastases will be enrolled in this trial to evaluate the efficacy of Nivolumab plus Ipilimumab plus two cycles of platinum-based chemotherapy as first line treatment.

Read the detailed description

This is an open-label, non-randomised, phase II, multicenter clinical trial. The total sample size is 71 patients. The population to be included are stage IV or recurrent, non-small cell lung cancer patients with synchronous brain metastases.

Patients randomised will receive induction treatment with two cycles of platinum-based chemotherapy plus Nivolumab and Ipilimumab. At the end of induction treatment the patient with start maintenance with Nivolumab and Ipilimumab until disease progression, unacceptable toxicity, loss of clinical benefit as judged by the investigator or up to a maximum of 2 years of treatment

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.

Patient accrual is expected to be completed within 1.5 years, treatment is planned to extend for 1 year and the patients will be followed up for 2 years. The study will end once survival follow-up has concluded.

Keywords
Lung Diseases, Chemotherapy, Immunotherapy, Induction chemotherapy, Maintenance treatment, Nivolumab, Ipilimumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Lung Neoplasms, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabDrug

    Also called Yervoy

    Patients will receive Ipilimumab 1mg/Kg administered by IV infusion every 42 days (Q6W) until disease progression, unacceptable toxicity, loss of clinical benefit as judged by the investigator or up to a maximum of 2 years of treatment.

    Structure: is a fully human monoclonal antibody with two heavy chains and two kappa light chains linked together by way of disulfide bonds. The molecular weight is approximately 148 kDa and it exists in solution at a physiologic pH of 7.0.

    Route of administration: Intravenous infusion.

  • NivolumabDrug

    Also called Opdivo

    Patients will receive Nivolumab 360 mg administered by IV infusion every 21 days (Q3W) until disease progression, unacceptable toxicity, loss of clinical benefit as judged by the investigator or up to a maximum of 2 years of treatment.

    Structure: Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains and 2 identical light chains.

    Route of administration: Intravenous infusion.

  • CarboplatinDrug

    Also called Paraplatin

    Patients will receive Carboplatin AUC 5 or 6 administered by IV infusion every 21 days (Q3W), for 2 cycles.

    Structure: The cis-diamino (cyclobutane-1, 1 dicarboxylate) platin. Stability: 24 hours at ambient temperature in 5% glucose, glucosa or physiologic saline. It is recommended not to dilute with chlorinated solutions since this could affect the carboplatin.

    Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center.

  • CisplatinDrug

    Also called Cis-diamminedichloroplatinum, Platinol

    Patients will receive Cisplatin 75mg/m2 administered by IV infusion every 21 days (Q3W), for 2 cycles.

    Structure: (CAS No. 15663-27-1, MF-Cl2H6N2Pt; NCF-119875), cisplatinum, also called cis-diamminedichloroplatinum(II), is a metallic (platinum) coordination compound with a square planar geometry. It is a white or deep yellow to yellow-orange crystalline powder at room temperature.

    Stability: Do not store above 25°C. Do not refrigerate or freeze. Keep container in the outer carton to protect from light. Following dilution in 0.9% sodium chloride injection, chemical and physical in-use stability has been demonstrated for up to 14 days at 20°C.

    Route of administration: Intravenous infusion. Guidelines of Cisplatin administration: According to the standard of each center.

  • PaclitaxelDrug

    Also called Taxol

    Patients will receive Paclitaxel 200mg/m2 administered by IV infusion every 21 days (Q3W), for 2 cycles.

    Structure: A diterpene whose composition is: 5b, 20-epoxy-1, 2a, 4,7b, 10b, 13a-hexahidroxytax-11-en 9 one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)- N-benzoyl-3-phenylisoserine.

    Stability: Concentrations of 0.3-1.2 mg/ml in 5% dextrose or normal saline have demonstrated chemical and physical stability for more that 27 hours at ambient temperature (25ºC approximately). The intact vial must be stored between 15º and 25ºC.

    Guidelines of Paclitaxel administration: Paclitaxel must be administered by infusion over 3 hours in dextrose (D5W) or normal saline (NS). The concentration must not exceed 1.2 mg/ml.

  • PemetrexedDrug

    Also called Pemetrexed disodium; ALIMTA

    Patients will receive Pemetrexed 500mg/m2 administered by IV infusion every 21 days (Q3W), for 2 cycles.

    Structure: Pemetrexed disodium (ALIMTA®, pemetrexed) is a novel pyrrol [2,3 d]-pyrimidine based folic acid analogue.

    Route of administration: Intravenous infusion. Guidelines of Pemetrexed administration: According to the standard of each center

Study groups in NCT05012254
Study groupRoleWhat they receive
Induction treatment + MaintenanceExperimentalInduction: 2 cycles of platinum-based chemotherapy plus (Nivolumab + Ipilimumab): - Non-squamous NSCLC patients: Pemetrexed: 500 mg/m2 IV, Q3W Carboplatin: AUC 5 o 6 or Cisplatin: 75 mg/m2 IV, Q3W Nivolumab: 360 mg IV Q3W Ipilimumab: 1mg/kg IV Q6W 2 cycles will be administered at 21-day intervals (Q3W) for Pemetrexed, Carboplatin/Cisplatin and Nivolumab. Ipilimumab will be administered at 42 days interval (Q6W). - Squamous NSCLC patients: Paclitaxel: 200 mg/m2 IV, Q3W Carboplatin: AUC 5 o 6, Q3W Nivolumab: 360 mg IV, Q3W Ipilimumab: 1mg/kg IV, Q6W Maintenance: following two cycles of chemo-immunotherapy the patients will receive: Nivolumab: 360 mg IV, Q3W Ipilimumab: 1mg/kg IV, Q6W Immunotherapy will be administered until disease progression, unacceptable toxicity, loss of clinical benefit or up to a maximum of 2 years of treatment.
Receives: Drug: Ipilimumab; Drug: Nivolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From the date of the end of treatment until the date of last follow up, assessed up to 24 months

Secondary outcomes (3)

  1. To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS)

    PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria

    Measured: From the date of the end of treatment until the date of last follow up, assessed up to 24 months

  2. To evaluate the Overall Response Rate (ORR) of the treatment

    Intracranial ORR, defined as a complete response or partial response as determined by the investigator according to RANO for brain disease. Systemic ORR, defined as a complete response or partial response as determined by the investigator according to RECIST v1.1. criteria for systemic disease.

    Measured: From the date of the end of treatment until the date of last follow up, assessed up to 24 months

  3. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

    Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.

    Measured: From the subject's written consent to participate in the study through 100 days after the final administration of the drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2021
  2. Study start18 Nov 2021
  3. Primary completion15 Oct 2027 (estimated)
  4. Study completion15 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05012254
Sponsor's protocol ID
GECP 21/02_NIVIPI-Brain
Other IDs
2021-000425-27
Acronym
NIVIPI-Brain
Status last verified
Apr 2026
First submitted
12 Aug 2021
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab, Nivolumab and Carboplatin in people with Non Small Cell Lung Cancer and Brain Metastases, Adult, run by Fundación GECP at 18 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of intracranial clinical benefit (time frame: From the date of the end of treatment until the date of last follow up, assessed up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05012254.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.

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