Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1

NCT06649474 | Recruiting

• 2 other identifiers: RBHP 2023 JARY2023-A02427-38
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Oesogastric and pancreatic adenocarcinomas are poor-prognosis cancers. Incidence of pancreatic cancer drastically increases to such an extent that it will become the second cause of cancer's mortality by 2030. A major challenge is to optimize the therapies for localized setting, when oxaliplatin-based chemotherapy is the standard, before and after surgical excision. Because in 50% of cases oxaliplatin triggers a grade 2-3 sinusoidal obstruction syndrome (SOS) which increases post-operative morbidity, decreases histological response to chemotherapy, increases tumor recurrence, and aggravates the risk of chemotherapy-induced peripheral neuropathy (CIPN). There is an urgent need to better understand the biological processes involved in SOS, in order to prevent and treat it without stopping or reducing oxaliplatin administration. The biological link between oxaliplatin and SOS has not been described, but recent murine experiments argue for HMGB1 to be the mediator released after exposure to oxaliplatin and inducing SOS, and thereafter CIPN. To date, no biomarker is established between murine and patient analyses, and the release of HMGB1 after oxaliplatin treatment and its effect on hepatic parenchyma is not described in patients. Investigators hypothesized is that HMGB1 would also been increased in patients after oxaliplatin treatment, and correlated to the development of SOS and CIPN. If confirmed, personalized treatment will be possible to target this pathway. Therefore, investigators propose to dynamically explore this hypothesis in localized oesogastric and pancreatic cancer patients who will be routinely managed by an initial laparoscopy and post-oxaliplatin surgical excision.

Conditions

Pancreatic Cancer; Resectable Pancreatic Adenocarcinoma; Adenocarcinoma; Resectable Esophageal Cancer; Resectable Gastric or Gastroesophageal Junction Adenocarcinoma; Oesophagogastric Cancer

Keywords

resecable pancreatic, oesophageal, gastric or gastroesophageal junction adenocarcinoma.; Patients able to have a laparoscopy; chemotherapy before surgery

Outcome Measures

Primary Outcomes (1)

• Serum HMGB1 concentrations

  Assess Serum HMGB1 concentrations in two groups of patients : with grade 0 or 1 SOS and with grade ≥2 SOS, at two timepoints: before exploratory laparoscopy and before surgical excision to determinate the effect of HMGB1 on SOS development

  At exploratory laparoscopy and at the surgery

Secondary Outcomes (8)

• variation of serum HMGBI concentration (ng/ml)

  at the exploratory laparoscopy, at the first (Day1) and last cycle (assessed up to 75 days) of chemotherapy before surgery (each cycle=14 days) and at the surgery

• variation of serum RAGE (receptor of HMGBI) concentration

  at the exploratory laparoscopy, at the first (Day1) and last cycle (assessed up to 75 days) of chemotherapy before surgery (each cycle=14 days) and at the surgery

• sinusoidal obstruction syndrome (SOS) diagnosis

  before to began chemotherapy and from 15 to 21 days after the last cycle of chemotherapy before surgery

• sinusoidal obstruction syndrome (SOS) diagnosis

  before to began chemotherapy and from 15 to 21 days after the last cycle of chemotherapy before surgery

• Evaluated the chemotherapy-induced peripheral neuropathy (CIPN)

  at the first (Day1) and last cycle (assessed up to 75 days) of chemotherapy before surgery (each cycle=14 days); at the surgery and at the first cycle (D1) then last cycle (assessed up to 75 days) after surgery

Study Arms (1)

comparate the Serum HMGB1 concentrations between patients with grade <2 SOS and those with grade 2,3

OTHER

Biological: assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy

Interventions

assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy BIOLOGICAL

assess the serum HMGB1 concentrations

comparate the Serum HMGB1 concentrations between patients with grade <2 SOS and those with grade 2,3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG WHO Performance status = 0 or 1
• Signed and dated informed consent
• Patients with histological diagnosis of oesogastric or pancreatic adenocarcinoma
• Resectable tumors
• Patients able to have a laparoscopy
• In case of absence of peritoneal invasion on the laparoscopy, patient candidate to a chemotherapy schedule by FLOT or FOLFOX in perioperative setting for oesogastric adenocarcinoma, or FOLFIRINOX in perioperative setting for pancreatic adenocarcinoma
• Registration in a national health care system (CMU included)
• Patient speak and understand the french

You may not qualify if:

• Histology other than adenocarcinoma
• Metastatic disease
• History of previous treatment with oxaliplatine
• Patient with an non balanced progressive condition/disease (liver failure, renal failure (creatinine clearance \&lt;30mL/min), respiratory failure, congestive heart failure, myocardial infarction in the last 6 months, etc.),
• Patient on curative dose anticoagulant,
• Patient with complete dihydropyrimidine dehydrogenase deficiency (Uracilemia ≥ 150 ng/ml),
• Patient not operable for the pathology concerned,
• Pregnant or breastfeeding woman, woman of childbearing age who has not performed a pregnancy test before the procedure,
• Patient with legal incapacity (person deprived of liberty or under curatorship, stutorship, safeguard of justice),
• Patient who, for psychiatric, social, family or geographical reasons, cannot be followed and/or comply with the requirements of the study,,
• Discovery of peritoneal invasion during the peritoneal exploratory of the laparoscopy

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Estaing de Clermont-Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Marine JARY, MD

  CHU Estaing de Clermont Ferrand/FRANCE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marine JARY, MD

CONTACT

+33 4 73 75 05 08; mjary@chu-clermontferrand.fr

Brigitte GILLET

CONTACT

bgillet@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 50 patients with pancreatic adenocarcinoma and 50 patients with oesogastric adenocarcinoma

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: October 18, 2024
• Study Start: September 6, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: October 18, 2024

Record last verified: 2024-10

Locations

FR (1)