Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
Condition: Pancreatic Cancer
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Intervention: nal-IRI; 5 fluorouracil; Leucovorin; Oxaliplatin
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic cancer; MM-398; Metastatic pancreatic cancer; First line pancreatic cancer treatment

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