A study of irinotecan, fluorouracil, calcium folinate, zimberelimab, and domvanalimab for patients with metastatic gastro-enteropancreatic neuroendocrine carcinoma.

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What is this study about?

This study focuses on individuals with neuroendocrine carcinoma of gastro-enteropancreatic or unknown origin, which is a type of cancer that begins in the specialized cells of the digestive system or other organs that release hormones. The purpose of the study is to compare the effectiveness of different treatment combinations in people who have already received another form of therapy for this condition.

One group of participants will receive a combination of medications, including irinotecan, fluorouracil, calcium folinate, zimberelimab, and domvanalimab. These medications are administered through IV infusion, which means they are delivered directly into a vein. Another group will receive a treatment consisting of irinotecan, fluorouracil, and calcium folinate. This study will monitor how long participants live and how the cancer responds to these different drug combinations over time.

Who Can Join the Study?

Both men and women who are 18 years of age or older can participate.
Patients who have brain metastasis (cancer that has spread to the brain) that does not cause symptoms or has been treated before.
A diagnosis of poorly differentiated neuroendocrine carcinoma, which is a type of fast-growing cancer starting in the digestive system or bile ducts, or a cancer where the origin is unknown.
A tumor with a Ki-67 index greater than 20%, which is a marker that shows how fast the cancer cells are dividing and growing.
The cancer must be locally advanced (has grown into nearby tissues) or metastatic (has spread to other parts of the body).
The diagnosis must be confirmed by a specialized doctor called a pathologist through a central review process.
The patient must have already received a first-line chemotherapy treatment using specific medicines (cisplatin or carboplatin combined with etoposide) and must now require a second-line chemotherapy because the cancer has progressed.
Progression means the cancer has grown or spread after the initial treatment.
The patient must have at least one measurable target lesion, which is a tumor that is large enough to be clearly seen and tracked on medical scans.
The tumor must be located in an area that has not received irradiation (treatment using high-energy rays to kill cancer cells).
A general condition score (ECOG-PS) of 0 or 1, which means the patient is physically able to carry out most daily activities.
Patients of childbearing age must agree to use very effective contraception (methods to prevent pregnancy) during the study and for a set period after the medicine is finished.
Men who are sexually active must also agree to use effective contraception during and after the treatment period.
The patient must sign an informed consent form, which is a document explaining all details of the study before agreeing to join.
The patient must be covered by the National French social security system.

Who Cannot Join the Study?

You have a well differentiated neuroendocrine tumor, which is a type of slow-growing tumor that comes from specific cells in the body.
You have a dihydropyrimidine dehydrogenase (DPD) deficiency, a condition where the body lacks a specific enzyme needed to break down certain medications.
You have Gilbert’s syndrome, a common, harmless liver condition that causes a buildup of bilirubin in the blood.
Your bilirubin (a yellow substance in the blood) is too high, or your ASAT and ALAT (liver enzymes that indicate liver health) are too high, or your TP (total protein, which helps with blood clotting) is too low.
Your blood counts are too low, specifically neutrophils (white blood cells that fight infection), platelets (cells that help blood clot), or hemoglobin (a protein in red blood cells that carries oxygen).
You have long-term uncontrolled diarrhea or an intestinal occlusion, which is a blockage in the intestines.
You have a history of a severe allergic reaction to atropine, loperamide, or antiemetics (medicines used to prevent vomiting).
You are currently taking anticonvulsive agents (medicines used to prevent seizures) or CYP3A4 inducers (medicines that change how the body processes other drugs), unless you stopped them at least 7 days ago.
You require high doses of systemic corticosteroids (steroid medicines used to reduce inflammation) or immunosuppressive medications (drugs that lower the immune system), unless you stopped them 14 days ago.
You have an active autoimmune disease, which is a condition where the immune system attacks the body’s own healthy cells, and you have used strong medicines for it in the last 2 years.
You have a history of or currently have pneumonitis, which is inflammation of the lung tissue, that required steroid treatment.
You have previously received first-line chemotherapy (the first treatment given for cancer) other than specific drugs called cisplatin, carboplatin, or etoposide.
You have received a live attenuated vaccine (a vaccine using a weakened form of a germ) within the last 28 days.
You are currently receiving any other anticancer therapy, such as radiation, immunotherapy, or hormone treatments for cancer.
You have a known hypersensitivity, which is an allergy, to any of the study drugs or their ingredients.
You have a known immunodeficiency or HIV infection with a high amount of virus in the blood or a low count of CD4+ T-cells (a type of white blood cell).
You have hepatitis B or hepatitis C, which are infections that cause liver inflammation.
You have had a serious infection that required antibiotics within the last 14 days.
You have previously received immunotherapy, which is a type of treatment that helps the immune system fight cancer.
You have had another type of cancer that is still active within the last 2 years, except for certain easily curable skin or early-stage cancers.
You are pregnant or breastfeeding.
You are not using effective contraception (methods to prevent pregnancy).
You have any condition that would prevent you from finishing the study or signing the informed consent form (a document explaining the study before you agree to join).
You have brain metastasis, which means cancer has spread to the brain and is causing symptoms.
You have had any of the following uncontrolled diseases in the last 6 months: liver failure, renal insufficiency (kidney problems), respiratory distress (difficulty breathing), congestive heart failure, unstable angina (chest pain), myocardial infarction (heart attack), or arrhythmia (irregular heartbeat).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut Gustave Roussy	Villejuif	France
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
CHU Grenoble Alpes	La Tronche	France

Other Sites

Site Name	City	Country
Centre Hospitalier Universitaire Rouen	Rouen	France
Centre Hospitalier Universitaire De Poitiers	Poitiers	France
Hopital Beaujon	Clichy	France
Centre Hospitalier Prive Saint-Gregoire	Saint-Gregoire	France
Institut De Cancerologie Strasbourg Europe	STRASBOURG, Alsace	France
Centre Hospitalier Universitaire De Montpellier	Montpellier	France
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Centre Hospitalier Lyon Sud	Pierre Benite	France
Centre Hospitalier Universitaire De Caen Normandie	Caen	France
Czjcpa Hudtobcwjdj Uqiqbowlkcnwv Rhpaq	Reims	France
Crbkws Hhoylmhdeto Eb Uptrfaobkgmwa Dv Lnmsmwl	Limoges	France
Ctbkha Hlhfxyolbuv Ueraoztbbakda Dv Dimzt	Dijon	France
Aflebinsox Pakrgvcp Hmqldfzt Dv Mlnmtjztn	Marseille	France
Iybkaciq Pmqzbzwtyfdpjxs Cosebz Cumbuy	Marseille	France
Capqjt Ozgvs Lydbwls	Lille	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.12.2025

Trial locations

Investigated drugs:

Irinotecan is a type of chemotherapy drug that is given through a vein to help stop the growth of cancer cells.

Domvanalimab is an investigational therapy given through a vein that is designed to work with the body’s immune system to fight cancer.

Fluorouracil is a common chemotherapy medication administered through a vein to treat various types of cancer by interfering with the cancer cells’ ability to grow.

Zimberelimab is an investigational therapy given through a vein that helps the immune system recognize and attack cancer cells.

Calcium levofolinate is a vitamin-based substance given through a vein that is used alongside certain chemotherapy drugs to help make the treatment more effective and better tolerated by the body.

Investigated diseases:

Neuroendocrine carcinoma metastatic

Neuroendocrine carcinoma of gastro-enteropancreatic or unknown origin – This is a type of cancer that develops from neuroendocrine cells, which are specialized cells found in various organs. These cells are located primarily in the digestive tract and parts of the pancreas. The disease occurs when these cells undergo uncontrolled growth and form malignant tumors. As the condition progresses, the cancer cells can spread from their original site to other parts of the body. It is characterized by its aggressive nature compared to other neuroendocrine tumors.

Trial ID:

2024-519922-19-00

Protocol code:

69HCL24_0759

Trial Phase:

Therapeutic exploratory (Phase II)

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A study of irinotecan, fluorouracil, calcium folinate, zimberelimab, and domvanalimab for patients with metastatic gastro-enteropancreatic neuroendocrine carcinoma.

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?