study of nanoliposomal irinotecan (nal-iri)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma

Conditions: Pancreatic Cancer

Summary: 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.


Eligibility criteria:
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

Keywords: pancreatic cancer mm-398 metastatic pancreatic cancer first line pancreatic cancer treatment