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

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ClinicalTrials.gov Identifier: NCT02551991
Recruitment Status : Active, not recruiting
First Posted : September 16, 2015
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Ipsen

Brief Summary:

This is an open-label, phase 2 comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients with advanced pancreatic adenocarcinoma who have not received prior chemotherapy. This study will assess the following regimen:

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

The study will be conducted in two parts:

  1. Part 1a: a safety run-in as initial dose exploration
  2. Part 1b: dose expansion of the nal-IRI + 5FU/LV + oxaliplatin regimen

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: nal-IRI Drug: 5 fluorouracil Drug: Leucovorin Drug: Oxaliplatin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2015
Estimated Primary Completion Date : February 28, 2019
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: nal-IRI + 5-FU/LV + oxaliplatin Drug: nal-IRI
Other Name: MM-398

Drug: 5 fluorouracil
Other Name: 5-FU

Drug: Leucovorin
Drug: Oxaliplatin



Primary Outcome Measures :
  1. Safety by reporting the adverse events and serious adverse events [ Time Frame: Up to 18 months ]
  2. Determine dose limiting toxicities (DLT) [ Time Frame: Up to 28 Days post first treatment ]

    Evaluated across a range of oxaliplatin and Nal-IRI dose levels administered by evaluating dose limiting toxicities (DLTs) if the following adverse events occur within 28 days of Cycle 1 or 14 days after Cycle 2 of treatment:

    • grade 4 neutropenia not resolved within 7 days, or complicated by fever more or equal to 38.5 °C
    • grade 3 neutropenia with infection
    • grade 4 non-hematologic toxicity
    • any study related adverse event that leads to delay of the next scheduled treatment dose for more than 14 days


Secondary Outcome Measures :
  1. Pharmacokinetic Cmax of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    Cmax (Observed maximal (peak) concentration)

  2. Pharmacokinetic Cavg of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    Cavg (Average plasma concentration)

  3. Pharmacokinetic Cmin of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    Cmin (Minimum plasma concentration)

  4. Pharmacokinetic AUCt of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    AUCt (Area under the plasma concentration time curve within a dosage interval (0 to last measurable concentration))

  5. Pharmacokinetic CL of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    CL (apparent total body clearance of the drug from plasma after administration)

  6. Pharmacokinetic Vd of total irinotecan, SN-38 and oxaliplatin [ Time Frame: Day 1 Predose, Day 1 at 1.5 hours (irinotecan and SN-38 only), Day 1 at 5.5 hours, Day 3, Day 8, Day 15, Day 30 Post last dose ]
    Vd (apparent volume distribution after administration)

  7. Progression Free Survival (PFS) [ Time Frame: up to 16 weeks post first treatment ]
  8. Overall Survival (OS) [ Time Frame: up to 16 weeks post first treatment ]
    Duration from the date of enrolment/randomization to the time of death.

  9. Overall Response Rate (ORR) [ Time Frame: up to 16 weeks post first treatment ]
    Proportion of patients with Best overall response (BOR) characterized as either a Complete or Partial Response (CR or PR) relative to the total number of evaluable patients.

  10. Disease Control Rate (DCR) [ Time Frame: up to 16 weeks post first treatment ]
  11. Safety and adverse event profile [ Time Frame: up to 18 months ]
    The incidence of adverse events will be summarized by type of adverse event and severity. All patients who have received at least one dose of irinotecan liposome injection will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 CYP2C8 inhibitors 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551991


  Show 24 Study Locations
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Ipsen Medical Director Ipsen

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02551991     History of Changes
Other Study ID Numbers: MM-398-07-02-03
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 2018

Keywords provided by Ipsen:
Pancreatic cancer
MM-398
Metastatic pancreatic cancer
First line pancreatic cancer treatment

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Oxaliplatin
Irinotecan
Fluorouracil
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs