Not yet recruitingRare disease

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

Verified siteRegistered drugNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

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.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Study assignment
You will be assigned to one of two different treatment groups through a process called randomization, which means the assignment is made by chance.
Step 2
Treatment group 1
You will receive a combination of four medications through intravenous infusion, which is medicine delivered directly into a vein.
The first medication is irinotecan, administered at a dose of 180 mg/m2 (milligrams per square meter of body surface area).
The second medication is fluorouracil, administered at a dose of 2800 mg/m2.
The third medication is calcium levofolinate, administered at a dose of 200 mg/m2.
The fourth medication is zimberelimab, administered at a dose of 480 mg.
You will also receive domvanalimab through infusion at a dose of 1600 mg.
Step 3
Treatment group 2
You will receive a combination of three medications through intravenous infusion.
The first medication is irinotecan, administered at a dose of 180 mg/m2.
The second medication is fluorouracil, administered at a dose of 2800 mg/m2.
The third medication is calcium levofolinate, administered at a dose of 200 mg/m2.
Step 4
Monitoring and evaluation
The effectiveness of the treatment is monitored by measuring overall survival, which is the length of time from the start of the study that you remain alive.
The progress of the disease is tracked through progression-free survival, which measures the time from the start of the study until the disease gets worse or death occurs.
Doctors will use radiological evaluation, such as medical imaging, to determine the objective response rate, which shows if the tumor has shrunk or disappeared, and the disease control rate, which shows if the disease is stable.
The duration of any response to the treatment is recorded, known as duration of response.
Side effects are monitored and graded using a standard system called toxicity assessment.
Your own feedback regarding your health and well-being is collected through questionnaires.

Who can join the trial?

15 criteria

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 trial?

25 criteria

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).

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Verified
Assistance Publique Hopitaux De Marseille
Marseille, France
Verified
CHU Grenoble Alpes
La Tronche, France
Verified
Centre Hospitalier Et Universitaire De Limoges
Limoges, France

Trial locations

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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.

What is already known about the treatment

Irinotecan
This medication is an anticancer drug administered through an intravenous injection or infusion. It is a well-established treatment used to manage various types of cancer by preventing cancer cells from copying their DNA, which stops them from multiplying. Belonging to a group called topoisomerase inhibitors, it works by blocking a specific enzyme that helps manage DNA structure.
Domvanalimab
This is an investigational biological therapy given by intravenous injection or infusion. It is currently being studied in clinical trials for its potential to treat certain types of advanced cancers. As an immunotherapy agent, it works by targeting specific proteins on the surface of immune cells to help the body's natural defenses recognize and attack cancer cells.
Fluorouracil
This is a common chemotherapy medication that is delivered into the body through an intravenous injection or infusion. It is widely used in medical practice to treat many different types of solid tumors. This drug works by interfering with the production of DNA, which prevents cancer cells from growing and dividing.
Zimberelimab
This is an experimental immunotherapy medication that is administered via intravenous injection or infusion. It is currently under investigation in clinical research to determine its effectiveness against specific cancers. It functions by attaching to certain targets on immune cells, which helps stimulate the immune system to fight against tumor cells more effectively.
Calcium levofolinate
This substance is administered through an intravenous injection or infusion and is used alongside certain chemotherapy drugs. It is an established medical component used to enhance the effectiveness of treatments like fluorouracil while helping to protect healthy cells. It works by providing a specific form of vitamin B that assists in the metabolic processes required for the chemotherapy to function properly.

Investigated diseases

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.