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Neuroendocrine TumorsPhase 2NCT03980925

Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.

A Phase 2 study testing Nivolumab, Carboplatin and Etoposide in people with Neuroendocrine Tumors and Neuroendocrine Neoplasm, run by Grupo Espanol de Tumores Neuroendocrinos at 12 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, multi-centre, open label, non-randomized phase II study evaluating the efficacy and safety of nivolumab plus platinum-based chemotherapy in patients with advanced G3 NENs of the GEP tract or of UK origin. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Carboplatin and Etoposide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
12 sitesSpain
Study dates
11 Oct 2019to 9 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Confirmed G3 NENs originated in the gastroenteropancreatic tract (WHO 2010 classification). Patients with a G3 NEN of unknown primary will also be eligible for this trial.
  • Ki-67 >20% or mitotic rate > 20 per 10 High-power field (HPF).
  • Metastatic or locally advanced unresectable disease not amenable to treatment with curative intent.
  • No prior systemic treatment for advanced disease nor as adjuvant therapy.
  • Availability of fresh or archive formalin-fixed, paraffin-embedded tumor tissue for biomarker assessment.
  • Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as per RECIST 1.1.
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  • Adequate organ function as defined by the following criteria (within 7 days prior to enrollment):
  • absolute neutrophil count (ANC) ≥1500 cells/mm3
  • platelets ≥100,000 cells/mm3
  • hemoglobin ≥9.0 g/dL
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); in patients with liver metastases AST and ALT ≤5.0 x ULN
  • total bilirubin ≤1.5 x ULN
  • serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min.
  • Male or female, age ≥18 years.
  • Eastern cooperative oncology group (ECOG) performance status of 0-2.
  • Life expectancy of ≥12 weeks.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment initiation.
  • Highly effective contraception (i.e. methods with a failure rate of less than 1 % per year) for both fertile, sexually active male and female subjects. Highly effective contraception must be used 28 days prior to first trial treatment administration, for the duration of trial treatment, and at least for 60 days after stopping trial treatment.
  • Signed and dated informed consent document must be given according to international conference harmonisation (ICH)/ Good clinical practice (GCP), and national/local regulations indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrolment.

Who cannot join

  • The following endocrine tumor types may not be included: paraganglioma, adrenal, thyroid parathyroid or pituitary endocrine tumors. Large or small cell lung neuroendocrine carcinoma of the lung will also be excluded.
  • Prior therapy with any immune checkpoint inhibitor.
  • Major surgery, except diagnostic biopsy, in <4 weeks or radiation therapy <2 weeks prior to starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
  • Prior organ transplantation, including allogeneic stem-cell transplantation.
  • Prior history of non-infectious pneumonitis requiring steroids or current pneumonitis.
  • Systemic chronic steroid therapy (> 10 mg/day prednisone or equivalent) or other immunosuppressive agents or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of steroids for allergic reactions or management of immune-related adverse events is allowed. Topical, inhaled, nasal and ophthalmic steroids are also allowed.
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  • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
  • Known history of positive testing for Human Immunodeficiency Virus (HIV) infection, known history of or positive tests for Hepatitis B virus surface antigen (HBVsAg) or Hepatitis C ribonucleic acid (HCV RNA) indicating acute or chronic infection or other significant acute or chronic infections requiring medication at study entry.
  • Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease. (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
  • Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
  • A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment will not be allowed to enter the study. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, new york heart association (NYHA) class > III congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
  • Known hypersensitivity reactions to monoclonal antibodies (≥ grade 3 according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 [xliii] or any past medical history of anaphylaxis or uncontrolled asthma (i.e., 3 or more asthma characteristics partially controlled).
  • Any other prior malignancy within 5 years of study entry, with the exception of adequately treated in-situ carcinoma of the cervix, breast or uteri, or non-melanomatous skin cancer.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
  • Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 6 months after discontinuing study treatment The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for study entry.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Spain12 sites
  • Institut Català d'Oncologia Badalona

    Badalona, Barcelona

  • Vall d'Hebron University Hospital

    Barcelona

  • Institut Català d'Oncologia l'Hospitalet

    L'Hospitalet de Llobregat, Barcelona

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Ramón y Cajal

    Madrid

  • MD Anderson Cancer Madrid

    Madrid

  • Hospital Clínico Universitario Virgen de la Victoria

    Málaga

  • Hospital Universitario Central de Asturias

    Oviedo

  • Hospital Universitario Marqués de Valdecilla

    Santander

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

About this study

Official title: A Phase II Study of Platinum-doublet Chemotherapy in Combination With Nivolumab as First-line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic G3 Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.

This is a prospective, multi-centre, open label, non-randomized phase II study evaluating the efficacy and safety of nivolumab plus platinum-based chemotherapy in patients with advanced G3 NENs of the GEP tract or of UK origin.

Medical subject headings
Neuroendocrine Tumors, Gastro-enteropancreatic neuroendocrine tumor

What participants receive

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

  • NivolumabDrug

    Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin area under the curve (AUC5) Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase).

    At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase).

    Cycles are defined by 4 weeks or 28 days.

  • CarboplatinDrug

    Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin AUC5 Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase).

    At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase).

    Cycles are defined by 4 weeks or 28 days.

  • EtoposideDrug

    Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin AUC5 Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase).

    At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase).

    Cycles are defined by 4 weeks or 28 days.

Study groups in NCT03980925
Study groupRoleWhat they receive
Nivolumab + platinum-doublet chemotherapyExperimental1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until progression of the disease (PD), death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
Receives: Drug: Nivolumab; Drug: Carboplatin; Drug: Etoposide

What is being measured

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

  1. Overall Survival Rate at 12 Months

    Percentage of patients alive at 1-year from first dose of treatment.

    Measured: 12 months

Secondary outcomes (7)
  1. Overall Response Rate (ORR)

    Response to treatment according to RECIST 1.1 criteria or iRECIST 1.1 criteria assessed by computed tomography (CT) scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Throughout the study period, approximately 24 months

  2. Progression-free Survival (PFS) Rate

    Percentage of patients without progression of disease (PD) calculated from the date of treatment initiation with first-line chemotherapy and nivolumab until the date of first documentation of PD as per RECIST v1.1 or death.

    Measured: Throughout the study period, approximately 24 months

  3. Median Overall Survival

    Length of time between start of treatment and death

    Measured: 30 months

  4. Predictive Biomarkers

    Assess biochemical response in patients with baseline elevation of enolase and correlate it with clinical outcome.

    Measured: 30 months

  5. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Number and type of adverse events reported throughout the study period according to CTCAE 5.0 criteria.

    Measured: 30 months

  6. Median Progression-free Survival

    Length of time between date of evidenced response and progression of disease or death

    Measured: 30 months

  7. Duration of Response

    The percentage of patients achieving Complete Response, Partial Response or stable disease (SD)

    Measured: 30 months

Timeline

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

  1. First posted10 Jun 2019
  2. Study start11 Oct 2019
  3. Primary completion13 Feb 2023
  4. Study completion9 Jun 2023

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
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03980925
Sponsor's protocol ID
GETNE-T1913
Status last verified
Nov 2024
First submitted
7 Jun 2019
Last updated
13 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Riesco-Martinez MC, Capdevila J, Alonso V, Jimenez-Fonseca P, Teule A, Grande E, Sevilla I, Benavent M, Alonso-Gordoa T, Custodio A, Anton-Pascual B, Hernando J, Polo E, Castillo-Trujillo OA, Lamas-Paz A, Teijo A, Rodriguez-Gil Y, Soldevilla B, Garcia-Carbonero R. Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913). Nat Commun. 2024 Aug 8;15(1):6753. doi: 10.1038/s41467-024-50969-8.

    PubMed 39117670

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Carboplatin and Etoposide in people with Neuroendocrine Tumors and Neuroendocrine Neoplasm, run by Grupo Espanol de Tumores Neuroendocrinos at 12 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 19 inclusion and 17 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: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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?

Yes. Results are posted in the registry (first posted 13 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Survival Rate at 12 Months (time frame: 12 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 NCT03980925, which also lists 1 linked publication.

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 13 Jan 2025.

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