Capecitabine and Temozolomide as Adjuvant Therapy for Patients with Resected Stage I‑III Pancreatic Neuroendocrine Tumors

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What is this study about?

The study focuses on patients with Pancreatic NeuroEndocrine Tumors that have been surgically removed with clear margins (R0 resected) and are considered aggressive but well‑differentiated. After surgery, an adjuvant approach is being tested, meaning additional treatment given to lower the chance that the cancer comes back. The treatment being examined consists of two oral chemotherapy medicines, Capecitabine and Temozolomide, taken in six cycles. The purpose of the study is to compare this chemotherapy plus regular monitoring with monitoring alone to determine which strategy better prevents cancer recurrence.

Participants are randomly assigned to one of the two groups and are followed for several years. Those receiving chemotherapy will take the pills according to a schedule and then undergo active surveillance, which includes clinic visits, imaging tests, and questionnaires about symptoms and quality of life. The other group will have the same surveillance without chemotherapy. The study measures how long patients remain free of cancer, described as disease-free survival, as well as how long they live overall, described as overall survival, and tracks any side effects. Regular check‑ups occur monthly during the first year and then yearly thereafter.

1 randomization and baseline assessment

after you are enrolled, you are assigned to a treatment group by randomization.

a baseline visit is performed to record your health status before any medication is taken.

2 start of chemotherapy – cycle 1

you begin the first cycle of chemotherapy.

the prescribed medicines are:

capecitabine tablets, oral, dose 1500 mg per square meter of body‑surface area, taken as directed.

temozolomide capsules, oral, dose 200 mg per square meter of body‑surface area, taken as directed.

the exact schedule for taking each dose is given by the study team and is followed for the duration of the cycle.

3 subsequent chemotherapy cycles (2‑6)

after completing cycle 1, you repeat the same medication regimen for five additional cycles.

each new cycle follows the same dosing instructions for capecitabine and temozolomide as in cycle 1.

the total treatment consists of six cycles.

4 monthly safety monitoring during the first year

throughout the first year, you attend monthly visits to check for side effects.

these visits include a review of any symptoms and a standard toxicity assessment using the national cancer institute criteria.

5 quality of life questionnaires

at the baseline visit, then every three months during the first year, you complete questionnaires that measure quality of life.

the questionnaires used are the eortc qlq‑c30, the net‑specific eortc qlq‑ginet21, and the eq‑5d‑5l.

6 completion of chemotherapy and transition to active surveillance

after the sixth cycle, the chemotherapy phase ends.

you then enter active surveillance, during which no further chemotherapy is given.

7 annual follow‑up assessments

after the first year, you continue to be seen once a year for up to ten years.

each annual visit includes evaluation of disease status for disease‑free survival, overall survival, and repeat quality of life questionnaires.

Who Can Join the Study?

Have a confirmed diagnosis of a well differentiated neuro‑endocrine tumor of the pancreas, meaning a pathology test showed the tumor cells look relatively normal and are a specific type of hormone‑related cancer.
Be within four months after surgery (the early postoperative period).
Have had an R0 resection, which means the surgeon removed all visible tumor and the edges of the removed tissue are free of cancer.
Show no distant metastasis (no spread of cancer to other organs) and no leftover tumor at the original site, confirmed by clear imaging scans: a chest CT, an abdominal CT or MRI, and, if done before surgery, a negative PET scan using either DOTA‑peptide 68Ga or FDG.
Have an ECOG performance status of 0‑1, indicating you are fully active or able to do light work but not limited by illness.
Have never received systemic therapy (treatment that travels through the whole body, such as chemotherapy) before entering the study.
Be considered at intermediate to high risk of recurrence, based on the Ki67 level (a lab test that measures how quickly tumor cells are dividing) and tumor size or lymph‑node involvement, using the following rules:
- If Ki67 ≥ 10 % (high‑grade tumor).
- If Ki67 5‑9 % and the tumor is larger than 3 cm or lymph nodes are positive.
- If Ki67 3‑5 % and the tumor is larger than 3 cm and lymph nodes are positive.
- If Ki67 < 3 % and the tumor is larger than 3 cm, lymph nodes are positive, and there is either vascular emboli (cancer cells in blood vessels) or perineural invasion (cancer around nerves).
Have the eligibility confirmed by a multidisciplinary meeting of expert doctors (the regional RENATEN‑ENDOCAN board).
Be 18 years of age or older; there is no upper age limit.
Have adequate bone marrow reserve, shown by blood tests: hemoglobin > 8 g/dL, absolute neutrophil count ≥ 1500 per mm³, and platelets ≥ 80,000 per mm³.
Agree to use effective contraception:
- Women who could become pregnant must have a negative pregnancy test and use a reliable birth‑control method during treatment and for at least six months after.
- Men with a partner who could become pregnant must use a reliable birth‑control method for at least three months after treatment and avoid donating sperm during that time.
Provide a written, dated, and signed informed consent before any study procedures.
Be able to follow the study visits and required procedures.
Be covered by a social security system or similar health benefit.
Have a sample of the original tumor available so it can be classified by the WHO system and tested for MGMT status.
Have cancer staged as Stage I‑III according to the ENETS‑UICC 8th edition classification.

Who Cannot Join the Study?

Having a tumor that looks abnormal under the microscope and is classified as poorly differentiated (NEC) – these are more aggressive cancer cells.
Blood test shows serum albumin (a protein that helps keep fluid in blood vessels) less than 3.0 g/dL unless the prothrombin time (a test of blood clotting) is normal.
Currently taking another experimental medication that is being studied.
Still experiencing side effects or complications from the recent surgery.
Having an active or suspected serious illness (acute or chronic) that is not under control and could increase risk while taking the study drug, according to the doctor.
Having a deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD) or not having been tested for it.
Recent or ongoing use of the antiviral drug brivudine.
Known allergy or severe reaction (hypersensitivity) to the study medicines Capecitabine or Temozolomide, or to any of the inactive ingredients (excipients) in those drugs.
Having a tumor that contains both neuroendocrine and non‑neuroendocrine cancer cells, called mixed neuroendocrine‑non neuroendocrine tumor (MiNEN).
Having received treatment before surgery (neoadjuvant therapy) or having taken chemotherapy that is used for a different type of cancer.
Being pregnant or breastfeeding.
Having an ECOG performance status higher than 1, which means having significant limitation in daily activities.
Being younger than 18 years old.
Having a pancreatic neuroendocrine tumor that occurs as part of a genetic condition such as NF1, VHL, or MEN and already having other neuroendocrine tumors diagnosed.
Having had another cancer in the past, except for cured non‑melanoma skin cancer, cured early‑stage cervical cancer (in situ), or other cancers that have been treated and have shown no signs of disease for at least five years.
Having severe kidney problems, defined as a glomerular filtration rate (GFR) measured by the MDRD formula less than 30 mL/min, or having a kidney disease called nephrotic syndrome, or having serious liver problems such as liver enzymes (ALT/AST) more than 2.5 times the normal upper limit (or more than 5 times if the liver changes are due to the cancer) or a total bilirubin level more than 2.5 times the normal upper limit.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut De Cancerologie De Lorraine	Vandoeuvre Les Nancy	France
CHU de Rouen – Hôpital Charles Nicolle	Rouen	France
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Universitaire De Lille	Lille	France
Institut Gustave Roussy	Villejuif	France
Oncopole Claudius Regaud	Toulouse	France
Institut Curie – Site Paris	Paris	France

Other Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Caen Normandie	Caen	France
Centre De Lutte Contre Le Cancer Eugene Marquis	Rennes	France
Centre Hospitalier Universitaire De Nantes	Nantes	France
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Hopital Beaujon	Clichy	France
Hospital Edouard Herriot	Lyon	France
Iewaoeng Pwzejwygympynqn Cwzvcj Cifcxp	Marseille	France
Atrixpqncs Poclbajh Hrtvkmlp Dh Pvcgs	Paris	France
Cxpjym Hhceenwvksp Ufvzcrixuwqnz Dz Dvanl	Dijon	France
Adgevtwhgt Pawjdaxy Huzmowmx Dx Mzuxrjydj	Marseille	France
Cacexe Hwfmifdrayo Usaogdmfuzhwp Rulbp	Reims	France
Hrrgvujx Uufjqolawpkbmk Sermowrbnf &cgodpc Haynmgh ds Houdhvqvxjn	STRASBOURG, Alsace	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	25.07.2026

Trial locations

Investigated drugs:

Capecitabine is an oral chemotherapy medicine that is turned into a cancer‑killing drug inside the body. In this study it is taken by mouth to help stop any remaining cancer cells from growing after surgery for pancreatic neuroendocrine tumors.

Temozolomide is another oral chemotherapy drug that works by damaging the DNA of cancer cells, making it harder for them to multiply. In the trial it is given together with capecitabine to target any cancer cells that might still be present after the tumor has been removed.

Capecitabine‑Temozolomide chemotherapy is the combination of the two medicines taken together for six treatment cycles. This systemic chemotherapy is meant to treat the whole body, aiming to lower the chance that the cancer comes back after the pancreas tumor has been surgically removed.

Active surveillance means close, regular monitoring of the patient after surgery (and after the chemotherapy in the experimental group). Doctors check for signs that the cancer might return using scans, blood tests, and doctor visits, but no additional treatment is given unless the disease shows up again.

Pancreatic neuroendocrine tumor (PanNET) – Pancreatic neuroendocrine tumor (PanNET) is a growth that develops from hormone‑producing cells in the pancreas. These tumors are usually slow‑growing but can become more aggressive as they increase in size or spread to nearby lymph nodes. When the tumor is well differentiated and completely removed with clear margins (R0), it may still recur, especially in stages I to III. The disease can progress from a localized growth to involvement of regional structures and, eventually, to distant sites. Monitoring focuses on detecting any new growth after surgery.

Trial ID:

2025-523593-16-00

Protocol code:

CSET 2025 / 4242

Trial Phase:

Therapeutic confirmatory (Phase III)

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Capecitabine and Temozolomide as Adjuvant Therapy for Patients with Resected Stage I‑III Pancreatic Neuroendocrine Tumors

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?