Clinical trial NCT06068023: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ampullary Adenocarcinoma
Keywords: pancreatobiliary-type
intestinal-type
mixed/hybrid-type
adjuvant chemotherapy
CAPOX
FOLFIRINOX
Lead sponsor: Fondazione Poliambulanza Istituto Ospedaliero
Sponsor class: OTHER
Collaborators: name: Associazione Italiana per la Ricerca sul Cancro
First posted: 2023-10-05
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible patients are adult non-pregnant patients with a good WHO performance score and have (borderline) resectable non-metastatic ampullary cancer.

Brief summary: 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.

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.

Primary outcomes:
measure: Disease-free survival (3y)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (3y)
timeFrame: 3 years
measure: Disease-free survival (5y)
timeFrame: 5 years
measure: Overall survival (5y)
timeFrame: 5 years
measure: Quality of Life questionnaire (qualitative outcome)
timeFrame: 3 years
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
state: BS
Study officials:
affiliation: Fondazione Poliambulanza Instituto Ospedaliero
name: Moh'd Abu Hilal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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 gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012 Jul 11;308(2):147-56. doi: 10.1001/jama.2012.7352.
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citation: 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 the Unicancer-GI-PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.
citation: 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.
citation: 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 chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study. Br J Surg. 2020 Aug;107(9):1171-1182. doi: 10.1002/bjs.11555. Epub 2020 Apr 7.