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Trial record 18 of 38 for:    MM-398

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

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ClinicalTrials.gov Identifier: NCT03528785
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Centro Ricerche Cliniche di Verona

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.


Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Drug: Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid Phase 2

Detailed Description:

This is a study to determine the proportion of patients affected by resectable pancreatic cancer who achieve R0 resection after a perioperative 6-cycle chemotherapy, 3 pre- and 3 post-surgery, in the absence of disease progression or unacceptable toxicity.

All patients in the program will be identified by a unique identifier number assigned sequentially.

Patients will receive a treatment scheme of nal-IRI, oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) on Day 1 and Day 15 of each 28 day cycles.

C1D1 is a fixed day, C1D15 and Day 1 and Day 15 of all subsequent cycles should be performed with a window of ± 2 days.

Patients achieving stable disease or better will undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy, patients will receive an additional 3 cycles of nal-IRI, oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) treatment in the absence of disease progression or unacceptable toxicity.

Tumor responses will be assessed after 3 cycles of preoperative treatment and after 3 cycles of postoperative treatment or sooner if the treating physician suspects disease progression based on clinical signs and symptoms. All treatment decisions will be based on the local radiologist and/or treating physician assessment of disease status.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Liposomial IrinoTecan (Nal-IRI) With 5-Fluorouracil, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer "nITRo Trial
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: Single Arm
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
  • 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




Primary Outcome Measures :
  1. Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU) [ Time Frame: 4-8 weeks after the completion of 3 courses of treatment ]
    Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)


Secondary Outcome Measures :
  1. To determine 2-year overall survival (OS) [ Time Frame: 2 years ]
    (OS)

  2. determine disease-free survival (DFS) [ Time Frame: through study completion, an average of 2 years ]
    (DFS)

  3. estimate frequency and severity of adverse events associated with chemotherapy [ Time Frame: through study completion, an average of 2 years ]
    AE

  4. determine overall response rate (ORR) following preoperative chemotherapy [ Time Frame: through study completion, an average of 2 years ]
    ORR

  5. estimate proportion of patients going to surgery for resection after preoperative chemotherapy [ Time Frame: through study completion, an average of 2 years ]
    estimate proportion of patients going to surgery for resection after preoperative chemotherapy

  6. estimate pathologic response rate (pCR) [ Time Frame: through study completion, an average of 2 years ]
    (pCR)

  7. assess lymph node status [ Time Frame: through study completion, an average of 2 years ]
    assess lymph node status

  8. assess surgical mortality [ Time Frame: through study completion, an average of 2 years ]
    assess surgical mortality

  9. assess surgical morbidity [ Time Frame: through study completion, an average of 2 years ]
    assess surgical morbidity



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. Able to understand and provide written informed consent.
  2. ≥ 18 years of age.
  3. Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas.
  4. 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.
  5. The primary tumor must be surgically resectable, defined as:

    1. no involvement (abutment or encasement) of the major arteries (celiac, common hepatic and/or superior mesenteric artery);
    2. no involvement or <180° interface between tumor and vessel wall of the portal vein, superior mesenteric vein and/or portal vein/splenic vein confluence.
  6. Adequate hepatic, renal and hematological function.

Exclusion Criteria:

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

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): NCT03528785


Contacts
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Contact: stefano Milleri, Dr +390458126619 stefano.milleri@crc.vr.it

Locations
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Italy
Centro Ricerche Cliniche Recruiting
Verona, Italy, 37134
Contact: Stefano Milleri, Dr.    +390458126619    stefano.milleri@crc.vr.it   
Contact: Giorgia Barbiero, Dr.    +390458126562    giorgia.barbiero@crc.vr.it   
Principal Investigator: Davide Melisi, Dr         
Sponsors and Collaborators
Centro Ricerche Cliniche di Verona
Investigators
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Study Director: stefano milleri, Dr centro ricerche cliniche

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Responsible Party: Centro Ricerche Cliniche di Verona
ClinicalTrials.gov Identifier: NCT03528785     History of Changes
Other Study ID Numbers: CRC2017_01
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
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

Keywords provided by Centro Ricerche Cliniche di Verona:
Pancreatic Adenocarcinoma
Liposomial IrinoTecan
nal-IRI
Resectable pancreatic cancer

Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Oxaliplatin
Irinotecan
Fluorouracil
Camptothecin
Levoleucovorin
Leucovorin
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents