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

Sponsor

Fondazione Poliambulanza Istituto Ospedaliero (Other)

Overall Status

Recruiting

CT.gov ID

NCT06068023

Collaborator

Associazione Italiana per la Ricerca sul Cancro (Other)

400

Enrollment

Location

Anticipated Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ampullary Adenocarcinoma	Drug: Folfirinox Drug: Capox

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2028

Anticipated Study Completion Date :

Jul 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Intestinal-type ampullary adenocarcinoma intervention This cohort consist of patients with intestinal-type ampullary adenocarcinoma who are able to receive adjuvant chemotherapy.	Drug: Capox or 8 CAPOX cycles (Arm 1) every 3 weeks. Other Names: Capecitabine and oxaliplatin
Intestinal-type ampullary adenocarcinoma control This cohort consist of patients with intestinal-type ampullary adenocarcinoma who are able to receive adjuvant chemotherapy but due to logistics or patient preference, are not willing to receive adjuvant chemotherapy.
Pancreatobiliary/mixed-type ampullary adenocarcinoma intervention This cohort consist of patients with Pancreatobiliary/mixed-type ampullary adenocarcinoma who are able to receive adjuvant chemotherapy.	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 research. FOLFIRINOX regimen mirrors the modified version from the ACCORD/PRODIGE trial for metastatic pancreatic cancer. This trial adapts mFOLFIRINOX for standard practice. Other Names: leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin.
Pancreatobiliary/mixed-type ampullary adenocarcinoma control This cohort consist of patients with Pancreatobiliary/mixed-type ampullary adenocarcinoma who are able to receive adjuvant chemotherapy but due to logistics or patient preference, are not willing to receive adjuvant chemotherapy.

Outcome Measures

Primary Outcome Measures

Disease-free survival (3y) [3 years]
Disease-free survival (DFS) refers to the length of time after treatment for a disease in months, such as cancer, during which no signs or symptoms of the disease recur or progress. It is a crucial measure in assessing the effectiveness of a treatment regimen in preventing the return of the disease. In cancer contexts, DFS focuses on the period without disease recurrence or progression, highlighting the success of the treatment in controlling the illness.

Secondary Outcome Measures

Overall survival (3y) [3 years]
Overall survival (OS) is a critical medical outcome that measures the length of time in months from the start of treatment or diagnosis until a patient's death due to any cause. It provides a comprehensive view of the effectiveness of a treatment or intervention in extending a patient's life expectancy. OS is a fundamental endpoint in clinical trials and medical research, reflecting the real-world impact of medical strategies on patients' survival outcomes.
Disease-free survival (5y) [5 years]
Disease-free survival (DFS) refers to the length of time in months after treatment for a disease, such as cancer, during which no signs or symptoms of the disease recur or progress. It is a crucial measure in assessing the effectiveness of a treatment regimen in preventing the return of the disease. In cancer contexts, DFS focuses on the period without disease recurrence or progression, highlighting the success of the treatment in controlling the illness.
Overall survival (5y) [5 years]
Overall survival (OS) is a critical medical outcome that measures the length of time in months from the start of treatment or diagnosis until a patient's death due to any cause. It provides a comprehensive view of the effectiveness of a treatment or intervention in extending a patient's life expectancy. OS is a fundamental endpoint in clinical trials and medical research, reflecting the real-world impact of medical strategies on patients' survival outcomes.
Quality of Life questionnaire (qualitative outcome) [3 years]
Quality of life (QoL) is an essential outcome measure in clinical trials that assesses the overall well-being and satisfaction of patients throughout the course of a medical intervention or treatment. It encompasses various physical, emotional, social, and functional aspects of a patient's life, beyond just medical outcomes. QoL assessments provide valuable insights into how a treatment affects patients' daily functioning, emotional state, pain levels, social interactions, and overall sense of health and happiness. The questionnaires utilized in the ADAPTA study are the EQ-5D and the QLQ-C30.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.