Back to results

Nalirinox Neo-pancreas RAS Mut ctDNA Study

Primary Purpose

Resectable Pancreatic Ductal Adenocarcinoma

Status

Active

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

NALRINOX combination

About this trial

This is an interventional treatment trial for Resectable Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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.

Exclusion Criteria:

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)
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.

Sites / Locations

Hestia Duran I Reynals
Hospital Universitario Madrid Sanchinarro
Hospital Universitari Vall D'Hebron

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NALIRINOX treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

R0 resection

1-year survival and Overal survival (OS) in baseline KRAS+ and KRAS- subjects

Progression Free Survival (PFS)

Assessment of the proportion of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Assessment of the number of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Impact on R0 resection for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Impact on histological tumour response for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Impact on PFS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Impact on 1-year survival for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Impact on OS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX

Number of AEs and SAEs (according to CTCAE) to describe the safety profile of the neoadjuvant NALIRINOX scheme

Full Information

NCT ID

NCT04010552

First Posted

July 3, 2019

Last Updated

August 1, 2022

Sponsor

Fundación de investigación HM

Collaborators

Syntax for Science, S.L

1. Study Identification

Unique Protocol Identification Number

NCT04010552

Brief Title

Nalirinox Neo-pancreas RAS Mut ctDNA 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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 1, 2019 (Actual)

Primary Completion Date

August 2023 (Anticipated)

Study Completion Date

November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundación de investigación HM

Collaborators

Syntax for Science, S.L

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Resectable Pancreatic Ductal Adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NALIRINOX treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

NALRINOX combination

Intervention Description

NALRINOX: combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin

Primary Outcome Measure Information:

Title

Time Frame

8 weeks after surgical intervention

Secondary Outcome Measure Information:

Title

R0 resection

Time Frame