Adjuvant Trial in Pancreatic Neuroendocrine Tumors (ADJUPANET)

First Adjuvant Trial in Locally Resected Aggressive Pancreatic Neuroendocrine Tumors: a Randomized Phase III Investigating the Efficacy of Systemic Chemotherapy

ADJUPANET is an open label, double arm, multicenter, phase 3 trial that aims to investigate the efficacy of systemic chemotherapy in locally resected aggressive pancreatic neuroendocrine tumors. The two arms of patients are the following : i. control arm : active surveillance only, standard of care. ii. experimental arm : adjuvant chemotherapy with 6 cycles of CAPECITABINE-TEMOZOLOMIDE (per os) and active surveillance. Patients enrolled in the experimental arm will receive Capecitabine CAPECITABINE per os 750 mg/m² (twice a day: D1 to D14) D1=D28 and TEMOZOLOMIDE per os 200 mg/m² (once a day: D10 to D14) D1=D28.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Neuroendocrine Tumors; Pancreatic Neuroendocrine Tumors (pNET)
• Intervention / Treatment: Other: Active surveillance; Drug: Adjuvant chemotherapy with Capecitabine-Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Eric BAUDIN, MD; Phone Number: 33 01 42 11 42 44; Email: Eric.BAUDIN@gustaveroussy.fr
• Study Contact Backup: Name: Matthieu FARON, MD; Phone Number: 33 01 42 11 65 79; Email: Matthieu.FARON@gustaveroussy.fr

Study Locations

• France
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94800
      • Gustave Roussy
      • Contact: Matthieu FARON, MD; Phone Number: +33 01 42 11 65 79; Email: Matthieu.FARON@gustaveroussy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically proven well differentiated neuro-endocrine tumour of the pancreas by local teams
2. Availability of the primary tumor specimen, allowing accurate WHO classification and determination of MGMT status
3. Stage I-III based ENETS-UICC 8th classification
4. Early postoperative context (≤ 4 months)
5. R0 resection
6. Absence of distant metastasis or local tumor remnant as defined by a negative post-operative thorax CT and -abdomen CT or MRI and negative (best of DOTA-peptide 68Ga or, FDG) PET imaging if performed preoperatively
7. ECOG 0-1
8. No prior systemic therapy

9. Intermediate to high risk of recurrence as defined by the following situations:

   • Ki67 ≥ 10% (i.e.: Grade 3 or high Ki67 Grade 2)
   • Ki67 5-9% AND (tumor size > 3 cm OR Node positive)
   • Ki67 3-5% AND tumor size > 3 cm AND Node positive
   • Ki67 < 3% AND tumor size > 3 cm AND Node positive AND (Vascular Emboli OR perineural invasion)
10. Age ≥ 18 years at the time of consent, no superior limit
11. Adequate bone marrow reserve (hemoglobine > 8 g/dL, absolute neutrophils count ≥ 1500/mm³ and platelets ≥ 80 000/mm³)
12. Effective contraception
13. Written, dated and signed informed consent by the patient prior to any specific protocol procedure
14. Ability to comply with the protocol procedures
15. Patient affiliated to a social security system or beneficiary of the same

Exclusion Criteria:

1. Poorly differentiated tumours (NEC)
2. Mixed NeuroEndocrine Non NeuroEndocrine tumors (MiNEN)
3. Neoadjuvant treatment or treatment with chemotherapy regimen used for another malignancy
4. Pregnant women or breastfeeding women
5. ECOG performance status > 1
6. Age < 18 years
7. PanNET arising in a genetic syndrome with other NETs already diagnosed (NF1, VHL or MEN)
8. History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years
9. Severe renal insufficiency (measured GFR according to MDRD < 30 ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST > 5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.5 x ULN)
10. Serum albumin < 3.0 g/dL unless prothrombin time is within the normal range
11. Current treatment with another investigational drug
12. Unrecovered toxicity from surgery
13. Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the Investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study
14. Dihydropyrimidine dehydrogenase (DPD) deficiency or not done
15. Recent or concomitant treatment with brivudine
16. Hypersensitivity to Capecitabine or Temozolomide or to any of the excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Active surveillance only	Other: Active surveillance; Active surveillance according to the European Society for Medical Oncology (ESMO) and French Thesaurus National de Cancérologie Digestive (TNCD) guidelines with every 3 months for 2 years, every 4 months for 1 year and then every 6 months for 2 years: Evaluation and physical examination of a functional clinical syndrome (hormone- and tumor-related symptoms); Biological: chromogranin A and/or appropriate hormone biomarker if positive in the preoperative setting; Radiological: thoracic CT and abdomen CT or MRI
Experimental: Experimental group; Adjuvant chemotherapy with Capecitabine-Temozolomide followed by active surveillance	Other: Active surveillance; Active surveillance according to the European Society for Medical Oncology (ESMO) and French Thesaurus National de Cancérologie Digestive (TNCD) guidelines with every 3 months for 2 years, every 4 months for 1 year and then every 6 months for 2 years: Evaluation and physical examination of a functional clinical syndrome (hormone- and tumor-related symptoms); Biological: chromogranin A and/or appropriate hormone biomarker if positive in the preoperative setting; Radiological: thoracic CT and abdomen CT or MRI; Drug: Adjuvant chemotherapy with Capecitabine-Temozolomide; Chemotherapy with Capecitabine-Temozolomide (per os) for 6 cycles (6 months): CAPECITABINE per os 750 mg/m² (twice a day: D1 to D14) D1=D28; TEMOZOLOMIDE per os 200 mg/m² (once a day: D10 to D14) D1=D28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival (DFS)	time between randomization and the diagnosis of first recurrence or death, up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Specific survival	time from randomization to death due to disease progression, toxicity of the treatment or uncontrollable secretory syndrome, up to 5 years
Overall survival	time from randomization to death from any cause, up to 5 years
Toxicity assessment	at baseline, every month during the first year and then every year until the end of the study, up to 5 years
Time and pattern of recurrence	time from randomization to the detection of recurrence, up to 5 years
Quality of life assessment	evolution of the scores collected at baseline, every three months during one year, and then every year until the end of the study, up to 5 years

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2035
• Study Completion (Estimated): June 1, 2035

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CAPECITABINE; active surveillance; TEMOZOLOMIDE; stage I-III; R0 resected
• Additional Relevant MeSH Terms: Health Services Administration; Therapeutics; Drug Therapy; Quality of Health Care; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Combined Modality Therapy; Watchful Waiting; Chemotherapy, Adjuvant
• Other Study ID Numbers: 2025-523593-16-00; 2025 / 4242 (Other Identifier: Gustave Roussy CSET protocol number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No