NCT03986294

Second Line Treatment With Nal-IRI and S1 in Pancreatic Cancer

A Randomized Phase II Study of Second Line Treatment With Liposomal Irinotecan and S1 Versus Liposomal Irinotecan and 5-fluorouracil in Patients With Metastatic Pancreatic Cancer Who Failed on First Line Gemcitabine-based Chemotherapy

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer who underwent a therapy with gemcitabine.

Detailed description

The 5-year survival of patients with pancreatic cancer is less than 5%. Despite improvements over the past years with the introduction of FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin and leucovorin) and gemcitabine and nab-paclitaxel, the vast majority will have disease recurrence or progression within 6 months. Single-arm phase II studies have been conducted after gemcitabine-based therapy. Randomized clinical trial data are limited in this setting, but the conclusion up to recently was that there is no superior chemotherapeutic regimen after gemcitabine failure. However, the NAPOLI trial altered the treatment landscape. In this trial, patients with metastatic pancreatic cancer that progressed after treatment with gemcitabine-based chemotherapy received liposomal irinotecan (nal-IRI) either as single agent or in combination with 5-fluorouracil/ leucovorin (5-FU/LV), or 5-FU/LV alone. Patients treated with the combination of nal-IRI plus 5-FU/LV experienced a median survival of 6.1 months versus 4.2 months for the 5-FU/LV group. Recently, two studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study, S-1 demonstrated non-inferiority to gemcitabine in overall survival (OS) for advanced pancreatic cancer. In the second study, S-1 showed superiority to adjuvant chemotherapy with gemcitabine in OS. In addition to gemcitabine, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. Phase II studies of S-1 in patients with gemcitabine-resistant pancreatic cancer have demonstrated moderate activity with acceptable toxicity. Although there has been no confirmed evidence based on phase III trials, S-1 would be a feasible treatment option in this patient population. Objective: To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer, whereby the hypothesis is, based on studies conducted in the Asian population, that the combination of S-1 and nal-IRI will be superior compared to 5-FU/ LV and nal-IRI, in terms of progression free survival. Therefore, patients will be randomized, after the optimal dose of S-1 and nal-IRI has been determined in the run in phase, between S-1 in combination with nal-IRI and 5-FU/LV in combination with nal-IRI during the phase II part of the study.

Conditions

• Metastatic Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	S1 + Nal-IRI	S-1 will be given for 14 consecutive days, twice daily, followed by 2 weeks rest. Nal-IRI will be administered as an intravenous infusion on day 1 and 15. Courses of treatment will be repeated every 4 weeks.
DRUG	Nal-IRI+Leucovorin+5-FU	Nal-IRI 80 mg/m2 will be administered first, followed by LV 400 mg/m2, followed by 5-FU 2400 mg/m2 as an IV infusion over 46-hours on days 1-3. Each cycle consists of 14 days. Courses of treatment will be repeated every 2 weeks.

Timeline

• Start date: 2019-12-01
• Primary completion: 2022-01-01
• Completion: 2022-01-01
• First posted: 2019-06-14
• Last updated: 2021-01-15

Locations

1 site across 1 country: Netherlands