Adjuvant Trial in Pancreatic Neuroendocrine Tumors

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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
• Другое 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

Первичные конечные точки

• Disease-free survival (DFS) [Срок оценки: time between randomization and the diagnosis of first recurrence or death, up to 5 years]

Вторичные конечные точки (5)

• Specific survival [Срок оценки: time from randomization to death due to disease progression, toxicity of the treatment or uncontrollable secretory syndrome, up to 5 years]
• Overall survival [Срок оценки: time from randomization to death from any cause, up to 5 years]
• Toxicity assessment [Срок оценки: 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 [Срок оценки: time from randomization to the detection of recurrence, up to 5 years]
• Quality of life assessment [Срок оценки: 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]

Критерии участия

Критерии включения

• Pathologically proven well differentiated neuro-endocrine tumour of the pancreas by local teams
• Availability of the primary tumor specimen, allowing accurate WHO classification and determination of MGMT status
• Stage I-III based ENETS-UICC 8th classification
• Early postoperative context (≤ 4 months)
• R0 resection
• 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
• ECOG 0-1
• No prior systemic therapy
• 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)
• Age ≥ 18 years at the time of consent, no superior limit
• Adequate bone marrow reserve (hemoglobine > 8 g/dL, absolute neutrophils count ≥ 1500/mm³ and platelets ≥ 80 000/mm³)
• Effective contraception
• Written, dated and signed informed consent by the patient prior to any specific protocol procedure
• Ability to comply with the protocol procedures
• Patient affiliated to a social security system or beneficiary of the same

Критерии исключения

• Poorly differentiated tumours (NEC)
• Mixed NeuroEndocrine Non NeuroEndocrine tumors (MiNEN)
• Neoadjuvant treatment or treatment with chemotherapy regimen used for another malignancy
• Pregnant women or breastfeeding women
• ECOG performance status > 1
• Age < 18 years
• PanNET arising in a genetic syndrome with other NETs already diagnosed (NF1, VHL or MEN)
• 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
• 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)
• Serum albumin < 3.0 g/dL unless prothrombin time is within the normal range
• Current treatment with another investigational drug
• Unrecovered toxicity from surgery
• 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
• Dihydropyrimidine dehydrogenase (DPD) deficiency or not done
• Recent or concomitant treatment with brivudine
• Hypersensitivity to Capecitabine or Temozolomide or to any of the excipients

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Gustave Roussy — Villejuif

Идентификаторы

NCT: NCT07591493 · 2025-523593-16-00 · 2025 / 4242

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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