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Nalirinox Neo-pancreas RAS Mut ctDNA Study

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ClinicalTrials.gov Identifier: NCT04010552
Recruitment Status : Recruiting
First Posted : July 8, 2019
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Syntax for Science, S.L
Information provided by (Responsible Party):
Fundación de investigación HM

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.


Condition or disease Intervention/treatment Phase
Resectable Pancreatic Ductal Adenocarcinoma Drug: NALRINOX combination Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : November 2021

Arm Intervention/treatment
Experimental: NALIRINOX treatment
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.
Drug: NALRINOX combination
NALRINOX: combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. R0 resection [ Time Frame: Through the study completion (estimated to be 15 months) ]
  2. 1-year survival and Overal survival (OS) in baseline KRAS+ and KRAS- subjects [ Time Frame: Through the study completion (estimated to be 15 months) ]
  3. Progression Free Survival (PFS) [ Time Frame: Through the study completion (estimated to be 15 months) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or females, aged 18 years or older
  2. Histologically or cytologically confirmed diagnosis of PDAC
  3. Candidates for pancreatic cancer surgery (no comorbidities that can exclude for surgery)
  4. Life expectance of at least 12 months
  5. Carbohydrate antigen 19-9 (CA19-9) levels < 500 U/ml
  6. ECOG performance status ≤ 1
  7. Adequate bone marrow function:

    • Hemoglobin >9 g/dL
    • Platelets >100.000 µL
    • Absolute neutrophil count (ANC) >1500 µl
    • Serum albumin > 3 g/dL
  8. 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.
  9. Adequate renal function:

    - Clearance of creatinine (ClCr) >60 ml/min

  10. 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.
  11. Agree to participate and signed the ICF.

Exclusion Criteria:

  1. Patients with metastatic disease
  2. Patients ≥ 75 years.
  3. Uncontrolled coagulopathy
  4. Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity)
  5. Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past.
  6. Previous cytotoxic therapy within 36 months for other no-cancer disease (ie arthritis rheumatoid)
  7. 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
  8. Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule
  9. Human immunodeficiency virus (HIV) positivity, active Hepatitis B or Hepatitis C infection.
  10. 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.
  11. Pregnant or breast-feeding women.
  12. Any medical condition that, based on investigator's criteria, places the subject at risk, makes the subject ineligible or may jeopardize protocol compliance.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04010552


Contacts
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Contact: Antonio Cubillo, MD +34 917567800 acubillo@hmhospitales.com

Locations
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Spain
Hestia Duran I Reynals Not yet recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Contact: Berta Laquente, MD         
Principal Investigator: Berta Laquente         
Hospital Universitario Madrid Sanchinarro Recruiting
Sanchinarro, Madrid, Spain, 28050
Contact: Rafael Álvarez, MD         
Principal Investigator: Rafael Alvarez         
Hospital Universitari Vall D'Hebron Not yet recruiting
Barcelona, Spain, 80034
Contact: Teresa Macarulla, MD         
Principal Investigator: Teresa Macarulla         
Sponsors and Collaborators
Fundación de investigación HM
Syntax for Science, S.L
Investigators
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Study Director: Antonio Cubillo, MD Director

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Responsible Party: Fundación de investigación HM
ClinicalTrials.gov Identifier: NCT04010552     History of Changes
Other Study ID Numbers: FiHM006
First Posted: July 8, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms