Pancreatic AdenocarcinomaPhase 2nITRoNCT03528785
A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer
A Phase 2 study testing Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid in people with Pancreatic Adenocarcinoma, run by Centro Ricerche Cliniche di Verona at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma
- What is being tested?
- Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteItaly
- Study dates
- 2 Mar 2018to 1 Nov 2022
- 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
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Centro Ricerche Cliniche
Verona, 37134
Stefano Milleri, Dr., +390458126619, stefano.milleri@crc.vr.it
Giorgia Barbiero, Dr., +390458126562, giorgia.barbiero@crc.vr.it
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Pancreatic Adenocarcinoma
- Being tested
- Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid
- Keywords
- Pancreatic Adenocarcinoma, Liposomial IrinoTecan, nal-IRI, Resectable pancreatic cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic AcidDrug
- 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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4-8 weeks after the completion of 3 courses of treatment
Secondary outcomes (9)
To determine 2-year overall survival (OS)
(OS)
Measured: 2 years
determine disease-free survival (DFS)
(DFS)
Measured: through study completion, an average of 2 years
estimate frequency and severity of adverse events associated with chemotherapy
AE
Measured: through study completion, an average of 2 years
determine overall response rate (ORR) following preoperative chemotherapy
ORR
Measured: through study completion, an average of 2 years
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
Measured: through study completion, an average of 2 years
estimate pathologic response rate (pCR)
(pCR)
Measured: through study completion, an average of 2 years
assess lymph node status
assess lymph node status
Measured: through study completion, an average of 2 years
assess surgical mortality
assess surgical mortality
Measured: through study completion, an average of 2 years
assess surgical morbidity
assess surgical morbidity
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2018
- Study start2 Mar 2018
- Primary completion15 Nov 2021 (estimated)
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic 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
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro Ricerche Cliniche di Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- stefano milleri, Dr, Study director, centro ricerche cliniche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03528785
- Sponsor's protocol ID
- CRC2017_01
- Acronym
- nITRo
- Status last verified
- Jul 2021
- First submitted
- 9 Nov 2017
- Last updated
- 2 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPDs published
Publications
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.
PubMed 33403007
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03528785
- Acronym / sponsor ID
- nITRo / CRC2017_01
- Conditions
- Pancreatic Adenocarcinoma
- Keywords
- Pancreatic Adenocarcinoma, Liposomial IrinoTecan, nal-IRI, Resectable pancreatic cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- Centro Ricerche Cliniche di VeronaUniversity, hospital or other
- Study start
- 2 Mar 2018 (actual)
- Primary completion
- 15 Nov 2021 (estimated)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 18 May 2018 (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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic AcidAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| 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 | Drug | Single Arm |
Primary outcome
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)
9 secondary outcomes
To determine 2-year overall survival (OS)
Time frame: 2 years
determine disease-free survival (DFS)
Time frame: through study completion, an average of 2 years
estimate frequency and severity of adverse events associated with chemotherapy
Time frame: through study completion, an average of 2 years
determine overall response rate (ORR) following preoperative chemotherapy
Time frame: through study completion, an average of 2 years
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
Time frame: through study completion, an average of 2 years
estimate pathologic response rate (pCR)
Time frame: through study completion, an average of 2 years
assess lymph node status
Time frame: through study completion, an average of 2 years
assess surgical mortality
Time frame: through study completion, an average of 2 years
assess surgical morbidity
Time frame: through study completion, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2021.
- Derived from this study: PubMed 33403007Simionato 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.
- Individual participant dataSharing planned: Yes. all IPDs published
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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.
stefano milleri, Dr study director
centro ricerche cliniche
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid in people with Pancreatic Adenocarcinoma, run by Centro Ricerche Cliniche di Verona at 1 site in Italy.
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 8 inclusion and 10 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 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
Contact stefano Milleri, Dr (+390458126619, stefano.milleri@crc.vr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03528785, which also lists 1 linked publication.
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 2021.