The ADAPTA Study: ADjuvant chemotherAPy After Curative Intent resecTion of Ampullary Cancer.

Official title

The ADAPTA Study: ADjuvant chemotherAPy After Curative Intent resecTion of Ampullary Cancer. A Pan-European Prospective Multicenter Double Single Arm Cohort Study.

Overview

Ampullary adenocarcinoma (AAC) is a rare gastrointestinal cancer with varying survival rates, particularly the aggressive pancreatobiliary (PB) subtype. Adjuvant therapy benefits only PB and mixed subtype patients, while prospective studies are required for validation. A study proposes tailored adjuvant treatments (CAPOX for intestinal subtype, FOLFIRINOX for PB and mixed subtypes) based on histopathology to enhance survival, also exploring molecular sub-studies for deeper insights.

Detailed description

Background:

Ampullary adenocarcinoma(AAC) is rare. 5-year survival rates of 30% to 70% are seen after resection. This broad range of survival could be explained by the morphological heterogeneity in the three subtypes of AAC (pancreatobiliary, intestinal and mixed subtype), which complicates the prediction of individual prognosis and clinical decision making with regard to adjuvant therapy. To date there are no prospective studies to elucidate whether adjuvant chemotherapy improves survival in these patients.

Methods/design:

The ADAPTA study is a phase II prospective single arm multicenter cohort study including 200 patients with resected AAC (100 patients with intestinal subtype, and 100 with pancreatobiliary- and mixed subtype). All patients will be treated with CAPOX/ FOLFIRINOX respectively. Outcomes will be compared after propensity score matching to data of all patients in consecutive participating centers not treated according to the proposed regime.

Interventions

• Drug Folfirinox
  Patients meeting the criteria of post-operative adenocarcinoma of the ampulla of Vater will be enrolled, with adjuvant chemotherapy commencing within 8 weeks of recovery from surgery. Those undergoing palliative intent surgery or palliative chemotherapy are ineligible for the ADAPTA study. The ADAPTA study's adjuvant chemotherapy involves 8-12 FOLFIRINOX cycles (Arm 2) repeated 2 weeks. Given patient outcomes, 8 cycles of FOLFIRINOX are deemed sufficient due to completion challenges in prior re
• Drug Capox
  or 8 CAPOX cycles (Arm 1) every 3 weeks.

Primary outcome measures

• Disease-free survival (3y) [Time frame: 3 years]

Secondary outcome measures (4)

• Overall survival (3y) [Time frame: 3 years]
• Disease-free survival (5y) [Time frame: 5 years]
• Overall survival (5y) [Time frame: 5 years]
• Quality of Life questionnaire (qualitative outcome) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Adult patients with histologically or cytologically confirmed AAC with subtyping of pancreatobiliary/mixed subtype or intestinal subtype
• After curative resection for ampullary cancer without metastatic disease.
• WHO performance status 0 or 1
• Able and willing to receive adjuvant chemotherapy
• R0/ R1 resection
• Age ≥ 18 years
• Written informed consent

Exclusion criteria

• Prior radiotherapy, chemotherapy, or resection for AAC.
• Previous malignancy (excluding non-melanoma skin cancer), unless no evidence of disease and diagnosed more than 5 years before diagnosis of AAC.
• Pregnancy.
• R2 resection.
• Adjuvant chemotherapy started more than 12 weeks after surgery (aim to start within 8 weeks)
• Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
• Known hypersensitivity or contraindications against capecitabine, 5 FU, Irinotecan, or Oxaliplatin
• Inadequate organ functions, characterized by:

• Leucocytes (WBC) < 3.0 X 109/l
• Neutrophils < 1.500 (count per microliter of blood)
• Platelets < 100 x 109 /l
• Hemoglobin < 8 mmol/l
• Renal function: E-GFR < 50 ml/min (serum creatinine < 1.5 x UNL)
• cholestasis with elevated levels of bilirubin and/or alkaline phosphatase > 3x UNL (can be improved by biliary drainage if necessary)
• elevated transaminases (ALAT/ASAT) ≥ 5 x UNL
• hypoalbuminemia < 2.5 g/dl
• Inadequate coagulation status INR > 2 or Quick < 50%, aPTT >50 sec in the absence of any drugs interfering with coagulation such as acenocoumarin, warfarin, phenprocoumon, NMH or UFH.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Italy · 1 center

• Fondazione Poliambulanza — Brescia

Publications

• Zhou J, Hsu CC, Winter JM, Pawlik TM, Laheru D, Hughes MA, Donehower R, Wolfgang C, Akbar U, Schulick R, Cameron J, Herman JM. Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater. Radiother Oncol. 2009 Aug;92(2):244-8. doi: 10.1016/j.radonc.2009.05.006. Epub 2009 Jun 21. PMID 19541379
• Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Olah A, Rawcliffe CL, Verbeke CS, Campbell F, Buchler MW; European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabi PMID 22782416
• Bolm L, Ohrner K, Nappo G, Ruckert F, Zimmermann C, Rau BM, Petrova E, Honselmann KC, Lapshyn H, Bausch D, Weitz J, Sandini M, Keck T, Zerbi A, Distler M, Wellner UF. Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study. Pancreatology. 2020 Apr;20(3):433-441. doi: 1 PMID 31987649
• Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; Canadian Cancer Trials Group and PMID 30575490
• Overman MJ, Varadhachary GR, Kopetz S, Adinin R, Lin E, Morris JS, Eng C, Abbruzzese JL, Wolff RA. Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater. J Clin Oncol. 2009 Jun 1;27(16):2598-603. doi: 10.1200/JCO.2008.19.7145. Epub 2009 Jan 21. PMID 19164203
• Moekotte AL, Malleo G, van Roessel S, Bonds M, Halimi A, Zarantonello L, Napoli N, Dreyer SB, Wellner UF, Bolm L, Mavroeidis VK, Robinson S, Khalil K, Ferraro D, Mortimer MC, Harris S, Al-Sarireh B, Fusai GK, Roberts KJ, Fontana M, White SA, Soonawalla Z, Jamieson NB, Boggi U, Alseidi A, Shablak A, Wilmink JW, Primrose JN, Salvia R, Bassi C, Besselink MG, Abu Hilal M. Gemcitabine-based adjuvant ch PMID 32259295
• Uijterwijk BA, Lemmers DHL, Klei DS, Wilmink H, Ghidini M, Zaniboni A, Millella M, Scarpa A, Luchini C, Maisonneuve P, Besselink MG, Abu Hilal M. Adjuvant Chemotherapy After Curative Intent Resection of Ampullary Cancer (ADAPTA): Study Protocol for a Pan-European Prospective Multicenter Double Single Arm Trial. Am J Clin Oncol. 2026 Jul 1;49(7):342-349. doi: 10.1097/COC.0000000000001271. Epub 2026 PMID 41812337

Identifiers

NCT: NCT06068023 · ADAPTA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗