Resectable Pancreatic Ductal AdenocarcinomaPhase 2NCT04010552
Nalirinox Neo-pancreas RAS Mut ctDNA Study
A Phase 2 study testing NALRINOX combination in people with Resectable Pancreatic Ductal Adenocarcinoma, run by Fundación de investigación HM at 3 sites in Spain.
Trial summary
Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Resectable Pancreatic Ductal Adenocarcinoma
- What is being tested?
- NALRINOX combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 3 sitesSpain
- Study dates
- 1 May 2019to Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Male or females, aged 18 years or older
- Histologically or cytologically confirmed diagnosis of PDAC
- Candidates for pancreatic cancer surgery (no comorbidities that can exclude for surgery)
- Life expectance of at least 12 months
- Carbohydrate antigen 19-9 (CA19-9) levels < 500 U/ml
- ECOG performance status ≤ 1
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- Adequate bone marrow function:
- Hemoglobin >9 g/dL
- Platelets >100.000 µL
- Absolute neutrophil count (ANC) >1500 µl
- Serum albumin > 3 g/dL
- Adequate hepatic function:
- Aspartate aminotransferase (AST) <3 upper limits of normal (ULN)
- Alanine Aminotransferase (ALT) <3 ULN
- Total Bilirubin < 1.5 ULN. If values are > 1.5 external drainage with a stent is allowed.
- Adequate renal function:
- Clearance of creatinine (ClCr) >60 ml/min
- Sexually active men and women of childbearing potential must use efficient contraceptive methods. Contraceptive methods comprise: oral contraceptives, intrauterine devices, sexual abstinence, tubal ligation, IUD, barrier methods or another contraceptive considered appropriate by the investigator. Women of childbearing potential must have a negative serum pregnancy test before study entry.
- Agree to participate and signed the ICF.
Who cannot join
- Patients with metastatic disease
- Patients ≥ 75 years.
- Uncontrolled coagulopathy
- Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity)
- Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past.
- Previous cytotoxic therapy within 36 months for other no-cancer disease (ie arthritis rheumatoid)
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- Known or suspected reactions to any component of the study medication (5-FU/LV, nal- IRI or oxaliplatin) or to components of similar chemical or biologic composition
- Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule
- Human immunodeficiency virus (HIV) positivity, active Hepatitis B or Hepatitis C infection.
- Uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, myocardial infarction, or left ventricular ejection fraction (LVEF) < 50, among others, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breast-feeding women.
- Any medical condition that, based on investigator's criteria, places the subject at risk, makes the subject ineligible or may jeopardize protocol compliance.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Universitari Vall D'Hebron
Barcelona, 80034
Hestia Duran I Reynals
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Madrid Sanchinarro
PAU de Sanchinarro, Madrid, 28050
About this study
Official title: A Phase II Trial to Assess the Evolution of KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRINOX
Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases.
There are patients with clear criteria for surgical entry, others at the limit of the possibility of surgery, and patients with such advanced disease (either locally or with metastasis) that surgery is not indicated.
Read more
The objective of neoadjuvant chemotherapy treatment (received before surgery) is to reduce the tumor before surgery and reduce the risk of subsequent metastases and local recurrences, in borderline tumors or those resectable with high-risk criteria.
The FOLFIRINOX scheme, composed of 5-fluorouracil / folinic acid, oxaliplatin and irinotecan, is recommended as neoadjuvant treatment, but the response is still low. This study will use a modified FOLFIRINOX (NALIRINOX) regimen with a form of irinotecan attached to liposomes that allows greater action on tumor cells.
Mutations in the KRAS gene are associated with a greater growth capacity of tumor cells and are present in 90% of pancreatic cancers in advanced stages. They would be less frequent in earlier phases but little is known about the impact that chemotherapy treatment and subsequent surgery could have on the increase or decrease of these mutations, as well as their implication. The follow-up of these mutations with repeated pancreatic biopsies is not viable, but it can be monitored by simple blood samples in which the genetic material of the tumor can be analyzed.
- Being tested
- NALRINOX combination
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NALRINOX combinationDrug
NALRINOX: combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin
| Study group | Role | What they receive |
|---|---|---|
| NALIRINOX treatment | Experimental | Patients will be treated with NALIRINOX, a combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin. Treatment regimen will consist of 8 cycles of neoadjuvant NALIRINOX prior to surgery and trial duration is expected to be 24 months. Receives: Drug: NALRINOX combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with a good histological tumour response in the resected specimens after neoadjuvant chemotherapy with NALIRINOX and surgical removal according to the Ryan's classification in KRAS positive and negative patients
Measured: 8 weeks after surgical intervention
Secondary outcomes (11)
R0 resection
Measured: Through the study completion (estimated to be 15 months)
1-year survival and Overal survival (OS) in baseline KRAS+ and KRAS- subjects
Measured: Through the study completion (estimated to be 15 months)
Progression Free Survival (PFS)
Measured: Through the study completion (estimated to be 15 months)
Assessment of the proportion of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Assessment of the number of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Impact on R0 resection for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Impact on histological tumour response for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Impact on PFS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Impact on 1-year survival for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Impact on OS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Measured: Through the study completion (estimated to be 15 months)
Number of AEs and SAEs (according to CTCAE) to describe the safety profile of the neoadjuvant NALIRINOX scheme
Measured: Through the study completion (estimated to be 15 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study start1 May 2019
- Primary completionAug 2023 (estimated)
- Study completionNov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Resectable Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is a multicenter, single-arm, interventional, open-label, non-randomized, phase II clinical trial, to evaluate the association of KRAS mutational load and histological tumour response after chemotherapy treatment in patients with PDAC. Due to its single-arm design patients will be assigned to a single group (non-randomized) and there will be no masking (open-label).
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación de investigación HM
- Sponsor type
- University, hospital or other
- Collaborators
- Syntax for Science, S.L
- Responsible party
- Sponsor
- Investigators
- Antonio Cubillo, MD, Study director, Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04010552
- Sponsor's protocol ID
- FiHM006
- Status last verified
- Jul 2022
- First submitted
- 3 Jul 2019
- Last updated
- 2 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial to Assess the Evolution of KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRINOX
- ClinicalTrials.gov ID
- NCT04010552
- Acronym / sponsor ID
- FiHM006
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fundación de investigación HMUniversity, hospital or other
- Collaborators
- Syntax for Science, S.L
- Study start
- 1 May 2019 (actual)
- Primary completion
- Aug 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 8 Jul 2019 (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.
Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases.
There are patients with clear criteria for surgical entry, others at the limit of the possibility of surgery, and patients with such advanced disease (either locally or with metastasis) that surgery is not indicated.
The objective of neoadjuvant chemotherapy treatment (received before surgery) is to reduce the tumor before surgery and reduce the risk of subsequent metastases and local recurrences, in borderline tumors or those resectable with high-risk criteria.
The FOLFIRINOX scheme, composed of 5-fluorouracil / folinic acid, oxaliplatin and irinotecan, is recommended as neoadjuvant treatment, but the response is still low. This study will use a modified FOLFIRINOX (NALIRINOX) regimen with a form of irinotecan attached to liposomes that allows greater action on tumor cells.
Mutations in the KRAS gene are associated with a greater growth capacity of tumor cells and are present in 90% of pancreatic cancers in advanced stages. They would be less frequent in earlier phases but little is known about the impact that chemotherapy treatment and subsequent surgery could have on the increase or decrease of these mutations, as well as their implication. The follow-up of these mutations with repeated pancreatic biopsies is not viable, but it can be monitored by simple blood samples in which the genetic material of the tumor can be analyzed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is a multicenter, single-arm, interventional, open-label, non-randomized, phase II clinical trial, to evaluate the association of KRAS mutational load and histological tumour response after chemotherapy treatment in patients with PDAC. Due to its single-arm design patients will be assigned to a single group (non-randomized) and there will be no masking (open-label).
| Arm | Type | Receives |
|---|---|---|
| NALIRINOX treatment | Experimental | Drug: NALRINOX combinationPatients will be treated with NALIRINOX, a combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin. Treatment regimen will consist of 8 cycles of neoadjuvant NALIRINOX prior to surgery and trial duration is expected to be 24 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Male or females, aged 18 years or older
- Histologically or cytologically confirmed diagnosis of PDAC
- Candidates for pancreatic cancer surgery (no comorbidities that can exclude for surgery)
- Life expectance of at least 12 months
- Carbohydrate antigen 19-9 (CA19-9) levels < 500 U/ml
Key exclusion criteria (12 listed)
- Patients with metastatic disease
- Patients ≥ 75 years.
- Uncontrolled coagulopathy
- Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity)
- Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past.
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 |
|---|---|---|
| NALRINOX combinationNALRINOX: combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin | Drug | NALIRINOX treatment |
Primary outcome
Proportion of subjects with a good histological tumour response in the resected specimens after neoadjuvant chemotherapy with NALIRINOX and surgical removal according to the Ryan's classification in KRAS positive and negative patients
Time frame: 8 weeks after surgical intervention
11 secondary outcomes
R0 resection
Time frame: Through the study completion (estimated to be 15 months)
1-year survival and Overal survival (OS) in baseline KRAS+ and KRAS- subjects
Time frame: Through the study completion (estimated to be 15 months)
Progression Free Survival (PFS)
Time frame: Through the study completion (estimated to be 15 months)
Assessment of the proportion of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Assessment of the number of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Impact on R0 resection for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Impact on histological tumour response for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Impact on PFS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Impact on 1-year survival for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Impact on OS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX
Time frame: Through the study completion (estimated to be 15 months)
Number of AEs and SAEs (according to CTCAE) to describe the safety profile of the neoadjuvant NALIRINOX scheme
Time frame: Through the study completion (estimated to be 15 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2022.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Antonio Cubillo, MD study director
Director
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NALRINOX combination in people with Resectable Pancreatic Ductal Adenocarcinoma, run by Fundación de investigación HM at 3 sites in Spain.
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 19 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: status not confirmed, as of the sponsor's last update on 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects with a good histological tumour response in the resected specimens after neoadjuvant chemotherapy with NALIRINOX and surgical removal according to the Ryan's classification in KRAS positive and negative patients (time frame: 8 weeks after surgical intervention). 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 2 Aug 2022; AzTrials last refreshed its copy on 6 Nov 2026.