Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-Paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen:

• nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin

The study will be conducted in two parts:

Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting
• Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening
• At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1)
• ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening
• Adequate hematological, hepatic, renal and cardiac function
• Recovered from the effects of any prior surgery or radiotherapy
• Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)

Exclusion Criteria:

• Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
• Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present
• Uncontrolled Central Nervous System (CNS) metastases
• Clinically significant gastrointestinal disorder
• History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible
• Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin
• Use of strong CYP3A4 or inducers or presence of any other contra indications for irinotecan
• Pregnant or breast feeding
• Neuroendocrine or acinar pancreatic carcinoma
• Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening
• Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening
• Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression