AzTrials
AzTrials

Neuroendocrine CarcinomaPhase 2NIPINECNCT03591731

Nivolumab +/- Ipilimumab in Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)

A Phase 2 study testing Nivolumab and Ipilimumab in people with Neuroendocrine Carcinoma, run by Intergroupe Francophone de Cancerologie Thoracique at 7 sites in France.

Completed

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

Official record
Search all trials

Trial summary

Neuroendocrine tumors of the lung include the small cell carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC) and represent 20% of lung cancer. One of the only studies reported to date is reporting on a progression-free survival (PFS) and overall survival (OS) of 5.2 months and 7.7 months, respectively. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Carcinoma
What is being tested?
Nivolumab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
185 participants
Where
7 sitesFrance
Study dates
2 Jan 2019to 15 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Age ≥ 18 years.
  • WHO Performance status 0 - 1
  • Life expectancy > 12 weeks
  • Poorly differentiated neuroendocrine carcinoma (NEC): large and small cells for gastroenteropancreatic NEC (WHO 2010 classification) and only large cells for lung NEC (WHO 2015 classification), independently from PD-L1 expression status by tumor cells; mixed tumors with a prominent (>70%) NEC component are eligible
  • Tumor progression after one or two lines of treatment, including at least one line of platin-based chemotherapy
  • Unresectable locally advanced or metastatic stage
Show all 14Show fewer
  • Measurable disease according to RECIST 1.1 guidelines for solid tumors
  • Patients must have adequate organ function: creatinine clearance > 50 mL/min (Cockcroft formula), Neutrophiles count ≥ 1500/mm3; Platelets > 100 000/mm3 ; Hemoglobin > 9 g/dL; hepatic enzymes < 3 x ULN (upper limit of normal) with total bilirubin ≤ 2 × ULN except subjects with documented Gilbert's syndrome (≤ 5 × ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dL
  • Patients must have recovered from all toxicities associated with prior treatment, to acceptable baseline status, or a National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE v4.0) Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
  • Availability of tumor material for central review processes and translational research projects
  • Absence of any unstable systemic disease and any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.
  • Before patient inclusion, written informed consent must be given according to ICH/GCP, and national/local regulations.
  • Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 6 months after the final dose of investigational product. Men receiving nivolumab and who are sexually active with women of childbearing potential will be instructed to adhere to contraception for a period of 31 weeks after the last dose of nivolumab.
  • Patient must be affiliated to or a beneficiary of social security insurance.

Who cannot join

  • Patients <18 years old
  • Well-differentiated neuroendocrine tumor (NET G1 and G2 according to digestive WHO 2010 classification or typical/atypical carcinoid tumor according to lung WHO 2015 classification)
  • Small cell lung NEC (except as a minor <30% component in mixed tumors)
  • Known EGFR activating mutation or ALK or ROS1 rearrangement for lung NEC
  • Brain metastasis, except if surgically resected or treated with stereotaxic radiotherapy with no evolution within the 3 months before inclusion, and asymptomatic patient
  • Patients with a recent history of other malignancies except adequately treated non-melanoma skin cancer, and curatively treated in-situ cancer. Patients with history of solid tumors, including adenocarcinoma, treated in a curative way with or without chemotherapy and without any evidence of disease >2 years before randomisation can be included as well.
Show all 25Show fewer
  • History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Intranasal/inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Live attenuated vaccination administered within 30 days prior to randomization.
  • Known history of interstitial lung disease or CT-scan signs of interstitial lung disease.
  • Subjects with an active, known or suspected autoimmune disease, including systemic lupus erythematosis or Wegener's granulomatosis.
  • Note : Subjects with type I diabetes mellitis, or hypothyroidism are eligible if only requiring hormone replacement therapy.
  • Subjects with skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, are permitted to enroll.
  • Active or history of inflammatory or irritable bowel disease (eg, diverticulitis, colitis, Crohn's), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Note that diverticulosis is permitted.
  • Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:
  • known prior history of active tuberculosis-disease;
  • known acute or chronic B or C hepatitis by serological evaluation. Patients with serological sequelae of hepatitis (antibodies test serologically positive for virus) without hepatitis could be included.
  • known Human immunodeficiency virus infection.
  • Concurrent administration of any anti-cancer therapies (e.g., chemotherapy, other targeted therapy, experimental drug, etc.) other than those administered in this study
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 3 weeks prior to randomization;
  • Patients with a psychiatric history that hinders the comprehension of the information leaflet
  • Individual deprived of liberty or placed under the authority of a tutor.
  • Unwillingness to practice effective birth control. Pregnant or lactating women.
  • Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • Centre Hospitalier du Pays d'Aix

    Aix-en-Provence

  • CHU d'Amiens-Picardie

    Amiens

  • CHU d'Angers

    Angers

  • Auxerre - CH

    Auxerre, 89011

  • Avignon - CH

    Avignon

  • Lyon - Hôpital Edouard Herriot

    Lyon

  • Paris - Curie

    Paris

Other trials in France

About this study

Official title: A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs)

Neuroendocrine tumors of the lung include the small cell carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC) and represent 20% of lung cancer. One of the only studies reported to date is reporting on a progression-free survival (PFS) and overall survival (OS) of 5.2 months and 7.7 months, respectively.

Poorly differentiated gastroentero-pancreatic neuroendocrine carcinomas (GEP-NEC) represent a small sub-group of digestive NENs, according to the studies, 7 to 21% of patients. However, their prognosis is more negative, with the 5-year survival at less than 20%.

Many Phase III trials showed superiority in terms of efficacy and tolerance of nivolumab+/-ipilimumab versus standard chemotherapy in second-line treatment in metastatic solid tumors. Neuroendocrine tumors are considered as rare disease without therapeutic guidelines in this setting. The French academic oncology groups (IFCT, FFCD and GERCOR) have the opportunity to recruit a sufficient number of patients, in a reasonable period of time, to provide a proof-of-concept of the safety and efficacy of nivolumab+/-ipilimumab in this population.

Being tested
Nivolumab, Ipilimumab
Keywords
IFCT, NIPINEC, Neuroendocrine, FFCD, GERCOR
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

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

Study groups in NCT03591731
Study groupRoleWhat they receive
Arm A : monotherapy armExperimentalNivolumab administered IV
Receives: Drug: Nivolumab
Arm B : combination armExperimentalNivolumab administered IV followed by ipilimumab administered IV
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Objective response rate

    Number of patients with a best overall response of complete response (CR) or partial response (PR) assessed by investigators using validated criteria (i.e. RECIST 1.1) divided by the number of eligible patients.

    Measured: 8 weeks after randomization

Secondary outcomes (7)

  1. Objective response rate assessed by independent central review

    Number of patients with a best overall response of complete response (CR) or partial response (PR) assessed by independent central review using validated criteria (i.e. RECIST 1.1) divided by the number of eligible patients.

    Measured: 8 weeks after randomization

  2. Disease control rate assessed by independent central review

    Percentage of patients who will achieve complete response, partial response or stable disease

    Measured: 8 weeks after randomization

  3. Response duration

    Time between the date of the best overall response of partial or complete response until the date of progressive disease or death due to any cause.

    Measured: 24 months after randomization of the last subject

  4. Time to symptom deterioration

    Time between the date of treatment start and the date of event defined as the first documented symptom deterioration

    Measured: 24 months after randomization of the last subject

  5. Progression-free survival

    Time between the date of treatment start and the date of event defined as the first documented disease progression or death from any cause.

    Measured: 24 months after randomization of the last subject

  6. Overall Survival

    Time between the date of treatment start and the date of death from any cause.

    Measured: 24 months after randomization of the last subject

  7. Frequency of adverse events

    Measured: 24 months after randomization of the last subject

Timeline

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

  1. First posted19 Jul 2018
  2. Study start2 Jan 2019
  3. Primary completion9 Jul 2021
  4. Study completion15 Dec 2024

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
185 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03591731
Sponsor's protocol ID
GCO-001
Acronym
NIPINEC
Status last verified
Mar 2025
First submitted
9 Jul 2018
Last updated
1 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Walter TP, Mazieres J, Otto J, Lena H, Lepage C, Smith D, Madelaine J, Geriniere L, Egenod T, El Hajbi F, Ferru A, Clement-Duchene C, Madroszyk A, Brotelle T, Bouhier-Leporrier K, Desrame J, Ghiringhelli F, Paleiron N, Khalil A, Milot L, Chevallier O, Couvelard A, Lantuejoul S, Langlais A, Morin F, Duruisseaux M, Michel P, Louvet C, Westeel V, Girard N; IFCT-FFCD-GERCOR GCO. Nivolumab +/- Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial. J Clin Oncol. 2026 Apr 20;44(12):1120-1129. doi: 10.1200/JCO-25-01657. Epub 2026 Mar 3.

    PubMed 41774886

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Neuroendocrine Carcinoma, run by Intergroupe Francophone de Cancerologie Thoracique at 7 sites in France.

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 14 inclusion and 25 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 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Objective response rate (time frame: 8 weeks after randomization). 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 NCT03591731, 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 1 Apr 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in