Pancreatic CancerHEPATOXALINCT06649474
Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1
A study testing assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy in people with Pancreatic Cancer and Resectable Pancreatic Adenocarcinoma, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Resectable Pancreatic Adenocarcinoma, Adenocarcinoma
- What is being tested?
- assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 6 Sep 2024to 30 Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Histology other than adenocarcinoma
- Metastatic disease
- History of previous treatment with oxaliplatine
- History of systemic chemotherapy administration within 5 years prior to inclusion,
- Patient with an non balanced progressive condition/disease (liver failure, renal failure (creatinine clearance \<30mL/min), respiratory failure, congestive heart failure, myocardial infarction in the last 6 months, etc.),
- Patient on curative dose anticoagulant,
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brigitte GILLET contact
France1 site, 1 recruiting
- Recruiting
CHU Estaing de Clermont-Ferrand
Clermont-Ferrand, 63000
Marine JARY, MD, +33 4 73 75 05 08, mjary@chu-clermontferrand.fr
Brigitte GILLET, bgillet@chu-clermontferrand.fr
About this study
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.
Read more
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
- Being tested
- assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy
- Keywords
- resecable pancreatic, oesophageal, gastric or gastroesophageal junction adenocarcinoma., Patients able to have a laparoscopy, chemotherapy before surgery
- Medical subject headings
- Pancreatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapyBiological
assess the serum HMGB1 concentrations
| Study group | Role | What they receive |
|---|---|---|
| comparate the Serum HMGB1 concentrations between patients with grade <2 SOS and those with grade 2,3 | Other | Not described Receives: Biological: assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At exploratory laparoscopy and at the surgery
Secondary outcomes (8)
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
Measured: 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
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: from exploratory laparoscopy to last cycle of chemotherapy after surgery assessed up to 10 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start6 Sep 2024
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 50 patients with pancreatic adenocarcinoma and 50 patients with oesogastric adenocarcinoma
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marine JARY, MD, Principal investigator, CHU Estaing de Clermont Ferrand/FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649474
- Sponsor's protocol ID
- RBHP 2023 JARY
- Other IDs
- 2023-A02427-38
- Acronym
- HEPATOXALI
- Status last verified
- Oct 2024
- First submitted
- 5 Sep 2024
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1
- ClinicalTrials.gov ID
- NCT06649474
- Acronym / sponsor ID
- HEPATOXALI / RBHP 2023 JARY
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 6 Sep 2024 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 50 patients with pancreatic adenocarcinoma and 50 patients with oesogastric adenocarcinoma
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- Histology other than adenocarcinoma
- Metastatic disease
- History of previous treatment with oxaliplatine
- History of systemic chemotherapy administration within 5 years prior to inclusion,
- Patient with an non balanced progressive condition/disease (liver failure, renal failure (creatinine clearance \<30mL/min), respiratory failure, congestive heart failure, myocardial infarction in the last 6 months, etc.),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapyassess the serum HMGB1 concentrations | Biological | comparate the Serum HMGB1 concentrations between patients with grade <2 SOS and those with grade 2,3 |
Primary outcome
Serum HMGB1 concentrations
Time frame: At exploratory laparoscopy and at the surgery
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
8 secondary outcomes
variation of serum HMGBI concentration (ng/ml)
Time frame: 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
Time frame: 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
Time frame: before to began chemotherapy and from 15 to 21 days after the last cycle of chemotherapy before surgery
sinusoidal obstruction syndrome (SOS) diagnosis
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: from exploratory laparoscopy to last cycle of chemotherapy after surgery assessed up to 10 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brigitte GILLET contact
Marine JARY, MD principal investigator
CHU Estaing de Clermont Ferrand/FRANCE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy in people with Pancreatic Cancer and Resectable Pancreatic Adenocarcinoma, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marine JARY, MD (+33 4 73 75 05 08, mjary@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum HMGB1 concentrations (time frame: At exploratory laparoscopy and at the surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2024.