Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2023-A02427-38 | Other Identifier | registration number with the French drug agency |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| comparate the Serum HMGB1 concentrations between patients with grade <2 SOS and those with grade 2,3 | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy | Biological | assess the serum HMGB1 concentrations |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| variation of serum HMGBI concentration (ng/ml) | mesurated the serum HMGB1 concentration (ng/ml) at several time of treatment of the patient then comparated these assess the dynamic variation of serum HMGB1 concentrations after oxaliplatin-based chemotherapy in oesogastric and pancreatic cancer patients with grade 0 or 1 SOS and with grade ≥2 SOS | 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marine JARY, MD | Contact | +33 4 73 75 05 08 | mjary@chu-clermontferrand.fr | |
| Brigitte GILLET | Contact | bgillet@chu-clermontferrand.fr |
| Name | Affiliation | Role |
|---|---|---|
| Marine JARY, MD | CHU Estaing de Clermont Ferrand/FRANCE | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Estaing de Clermont-Ferrand | Recruiting | Clermont-Ferrand | 63000 | France |
Not provided
50 patients with pancreatic adenocarcinoma and 50 patients with oesogastric adenocarcinoma
Not provided
Not provided
Not provided
Not provided
| variation of serum RAGE (receptor of HMGBI) concentration | mesurated the serum RAGE concentration (ng/ml) at several time of treatment of the patient then comparated these assess the dynamic variation of serum HMGB1 concentrations after oxaliplatin-based chemotherapy in oesogastric and pancreatic cancer patients with grade 0 or 1 SOS and with grade ≥2 SOS | 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 | compare SOS histology diagnosis (absent, mild, moderate, severe) with no invasive biological scores "APRI and FIB4"which use ASAT (U/L), ALAT(U/L), plaquettes (G/L) and the age (years) of the patient | before to began chemotherapy and from 15 to 21 days after the last cycle of chemotherapy before surgery |
| sinusoidal obstruction syndrome (SOS) diagnosis | compare SOS histology diagnosis (absent, mild, moderate, severe)) with splenic's volumetric measured by radiological's assessment | 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) | the CIPN will be evaluate by the investigator who used the CTCAEv5 classification. | 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 |
| Evaluated the chemotherapy-induced peripheral neuropathy (CIPN) | the CIPN will be evaluate by each patient who completed the CIPN20 questionnary | 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 |
| Evaluated the chemotherapy-induced peripheral neuropathy (CIPN) | the CIPN will be evaluate by each patient who completed the visual analog score for pain | 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 |
| Predictive value of HMGB1 for the development of SOS and CIPN | Correlate CIPN, neuropathic pain with SOS, HMGB1, and RAGE measurements | from exploratory laparoscopy to last cycle of chemotherapy after surgery assessed up to 10 month |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D000230 | Adenocarcinoma |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided