Dataset Information

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

ABSTRACT:

Background

Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status. liposomal irinotecan (Nal-IRI) is a novel nanoliposome formulation of irinotecan that accumulates in tumor-associated macrophages improving the therapeutic index of irinotecan and has been approved for the treatment of patients with metastatic pancreatic cancer after progression under gemcitabine-based therapy. Thus, it remains of the outmost urgency to investigate introduction of the most novel agents, such as nal-IRI, in perioperative approaches aimed at increasing the long-term effectiveness of surgery.

Methods

The nITRO trial is a phase II, single-arm, open-label study to assess the safety and the activity of nal-IRI with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin in the perioperative treatment of patients with resectable pancreatic cancer. The primary tumor must be resectable with no involvement of the major arteries and no involvement or <180° interface between tumor and vessel wall of the major veins. A total of 72 patients will be enrolled to receive a perioperative treatment of three cycles before and three cycles after surgical resection with nal-IRI 50?mg/m², oxaliplatin 60?mg/m², leucovorin 200?mg/m², and 5-fluorouracil 2400?mg/m2, days 1 and 15 of a 28-day cycle. The primary objective is to improve from 40% to 55% the proportion of patients achieving R0 resection after preoperative treatment.

Discussion

The nITRO trial will contribute to strengthen the clinical evidence supporting perioperative strategies in resectable pancreatic cancer patients. Moreover, this study represents a unique opportunity for translational analyses aimed to identify novel immune-related prognostic and predictive factors in this setting.

Trial registration

Clinicaltrial.gov: NCT03528785. Trial registration data: 1 January 2018Protocol number: CRC 2017_01EudraCT Number: 2017-000345-46.

SUBMITTER: Simionato F

PROVIDER: S-EPMC7745557 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

Simionato Francesca F Zecchetto Camilla C Merz Valeria V Cavaliere Alessandro A Casalino Simona S Gaule Marina M D'Onofrio Mirko M Malleo Giuseppe G Landoni Luca L Esposito Alessandro A Marchegiani Giovanni G Casetti Luca L Tuveri Massimiliano M Paiella Salvatore S Scopelliti Filippo F Giardino Alessandro A Frigerio Isabella I Regi Paolo P Capelli Paola P Gobbo Stefano S Gabbrielli Armando A Bernardoni Laura L Fedele Vita V Rossi Irene I Piazzola Cristiana C Giacomazzi Serena S Pasquato Martina M Gianfortone Morena M Milleri Stefano S Milella Michele M Butturini Giovanni G Salvia Roberto R Bassi Claudio C Melisi Davide D

Therapeutic advances in medical oncology 20200904

<h4>Background</h4>Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good perf ...[more]

PMID: 33403007

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Project description:IntroductionLiposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has shown clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on gemcitabine-based chemotherapy. However, its role in patients with mPAC previously treated with conventional irinotecan-containing chemotherapy has not been appropriately investigated.MethodsIn this retrospective analysis, patients with mPAC who received nal-IRI plus 5-FU/LV after conventional irinotecan-containing regimen between January 2017 and March 2020, were identified from two referral cancer centers in South Korea. The ratio of time to progression (TTP) with nal-IRI plus 5-FU/LV to TTP with conventional irinotecan (TTPr) was analyzed with respect to the duration and cumulative dose of conventional irinotecan treatment.ResultsIn total, 35 patients treated with nal-IRI plus 5-FU/LV after the irinotecan-containing regimen were analyzed. The median age was 58 years and 16 (46%) patients were male. The median duration of conventional irinotecan therapy was 4.6 months at a median cumulative dose of 1230 mg. The objective response rate of nal-IRI plus 5-FU/LV was 2.9%, and stable disease was achieved in 11 (31.4%) patients. During the median follow-up of 9.2 [95% confidence interval (CI): 7.8-10.5] months, the median progression-free survival (PFS) and overall survival (OS) were 2.0 (95% CI: 1.4-2.6) months and 4.4 (95% CI: 3.6-5.7) months, respectively. The 6-month PFS and OS rates were 16.3% and 37.5%, respectively. The median TTPr was 0.41 (range, 0.07-2.07), showing a negative correlation with the cumulative dose of prior irinotecan therapy (R = -0.37, p = 0.041). A tentative negative correlation between TTPr and duration of prior irinotecan therapy was observed (R = -0.35, p = 0.062). The most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%).ConclusionNal-IRI plus 5-FU/LV showed modest effectiveness and manageable toxicities for patients with mPAC previously treated with conventional irinotecan-containing chemotherapy. The cumulative dose of prior conventional irinotecan therapy may be inversely correlated with the effectiveness of nal-IRI plus 5-FU/LV.

Project description:PurposeTo verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).MethodsTRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).ResultsFrom September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P = .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in R0 resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).ConclusionThe intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC.

Dataset Information

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

Background

Methods

Discussion

Trial registration

Publications

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

Similar Datasets

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