A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer

NCT03528785 | Unknown Phase 2

• 1 other identifier: CRC2017_01
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Rational:Pancreatic cancer is a systemic disease at the time of diagnosis, even among patients with apparent localized disease. Surgical resection is the only potentially curative therapy for pancreatic cancer, but in patients who undergo surgery and postoperative therapy, metastatic relapse remains common and no more than 20% of patients achieve 5-year survival. Because of this aggressive biologic behavior, an increasing interest is growing about preoperative treatments in resectable pancreatic cancer. The combination chemotherapeutic regimen with irinotecan + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin (FOLFIRINOX) is an effective choice for first line treatment in patients affected by advanced pancreatic cancer, and in this setting it achieved a Disease Control Rate of 70.2 % (10). In this regard, FOLFIRINOX is currently explored as preoperative regimen in a number of clinical trials in resectable pancreatic cancer. A critical challenge in this field remains the introduction in these combination treatments of the most novel and effective agents such as nalIRI, in order to obtain a more profound tumor shrinkage, to increase the rate of R0 resections, to allow an early treatment of occult micrometastatic disease, and eventually, to improve survival in patients with resectable pancreatic cancer. This study proposal is designed to address this challenge. Preliminary results, collected during the Part 1 Dose Escalation of a current clinical trial performed in mPDAC, show that dose of nal-IRI: 60 mg/m2, Oxaliplatin: 60 mg/m2, 5-FU/LV: 2400/400 mg/m2 is safe.

Conditions

Pancreatic Adenocarcinoma

Keywords

Pancreatic Adenocarcinoma; Liposomial IrinoTecan; nal-IRI; Resectable pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)

  Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)

  4-8 weeks after the completion of 3 courses of treatment

Secondary Outcomes (9)

• To determine 2-year overall survival (OS)

  2 years

• determine disease-free survival (DFS)

  through study completion, an average of 2 years

• estimate frequency and severity of adverse events associated with chemotherapy

  through study completion, an average of 2 years

• determine overall response rate (ORR) following preoperative chemotherapy

  through study completion, an average of 2 years

• estimate proportion of patients going to surgery for resection after preoperative chemotherapy

  through study completion, an average of 2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

All patients will receive a treatment scheme of Irinotecan Liposomal Injection \[Onivyde\], oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) on Day 1 and Day 15 of each 28 day cycles.

Drug: Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid

Interventions

Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid DRUG

* Oxaliplatin 60 mg/m2 IV in 120 minutes) on Days 1 and 15 of each cycle * Irinotecan Liposomal Injection \[Onivyde\] (60 mg/m2 IV over 90 minutes) on Days 1 and 15 of each cycle * Levofolinic acid (200 mg/m2 IV over 30 minutes) on Days 1 and 15 of each cycle * 5FU (2.400 mg/m2 IV over 46 hours) on Days 1 and 15 of each cycle

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and provide written informed consent.
• ≥ 18 years of age.
• Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas.
• Patients must have measurable disease in the pancreas, with no evidence of metastatic disease on imaging of the chest, abdomen and pelvis (contrast-enhanced CT or MRI abdomen with contrast instead of abdominal CT); PET scans alone will not be adequate alternatives.
• The primary tumor must be surgically resectable, defined as:
• no involvement (abutment or encasement) of the major arteries (celiac, common hepatic and/or superior mesenteric artery);
• no involvement or \<180° interface between tumor and vessel wall of the portal vein, superior mesenteric vein and/or portal vein/splenic vein confluence.
• Adequate hepatic, renal and hematological function.

You may not qualify if:

• Serum total bilirubin ≥2 x ULN (biliary drainage is allowed for biliary obstruction).
• Severe renal impairment (CLcr ≤ 30 ml/min).
• Inadequate bone marrow reserves as evidenced by:
• ANC ≤ 1,500 cells/μl; or Platelet count ≤ 100,000 cells/μl; or Hemoglobin ≤ 9 g/dL
• KPS \< 60
• Patients who received previous chemotherapy or radiotherapy for pancreatic disease.
• Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
• Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea \> grade 2.
• Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months.
• NYHA Class III or IV congestive heart failure, ventricular

Sponsors & Collaborators

• Centro Ricerche Cliniche di Verona: lead

Study Sites (1)

Centro Ricerche Cliniche

Verona, 37134, Italy

RECRUITING

Related Publications (1)

• Simionato F, Zecchetto C, Merz V, Cavaliere A, Casalino S, Gaule M, D'Onofrio M, Malleo G, Landoni L, Esposito A, Marchegiani G, Casetti L, Tuveri M, Paiella S, Scopelliti F, Giardino A, Frigerio I, Regi P, Capelli P, Gobbo S, Gabbrielli A, Bernardoni L, Fedele V, Rossi I, Piazzola C, Giacomazzi S, Pasquato M, Gianfortone M, Milleri S, Milella M, Butturini G, Salvia R, Bassi C, Melisi D. A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial. Ther Adv Med Oncol. 2020 Sep 4;12:1758835920947969. doi: 10.1177/1758835920947969. eCollection 2020.

  PMID: 33403007 DERIVED

MeSH Terms

Interventions

irinotecan sucrosofate; Oxaliplatin; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• stefano milleri, Dr

  centro ricerche cliniche

  STUDY DIRECTOR

Central Study Contacts

stefano Milleri, Dr

CONTACT

+390458126619; stefano.milleri@crc.vr.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: May 18, 2018
• Study Start: March 2, 2018
• Primary Completion: November 15, 2021
• Study Completion: November 1, 2022
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: starting 6 months after publication

Locations

IT (1)