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MM-398 (Nanoliposomal Irinotecan, Nal-IRI) to Determine Tumor Drug Levels and to Evaluate the Feasibility of Ferumoxytol Magnetic Resonance Imaging to Measure Tumor Associated Macrophages and to Predict Patient Response to Treatment

This study is currently recruiting participants.
Verified September 2017 by Ipsen
Sponsor:
ClinicalTrials.gov Identifier:
NCT01770353
First Posted: January 17, 2013
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Ipsen
  Purpose
This is a Phase I study to understand the biodistribution of MM-398 and to determine the feasibility of using Ferumoxytol as a tumor imaging agent.

Condition Intervention Phase
Solid Tumors ER/PR Positive Breast Cancer Triple Negative Breast Cancer Metastatic Breast Cancer With Active Brain Metastasis Drug: Ferumoxytol followed by MM-398 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Study in Patients Treated With MM-398 (Nanoliposomal Irinotecan, Nal-IRI) to Determine Tumor Drug Levels and to Evaluate the Feasibility of Ferumoxytol Magnetic Resonance Imaging to Measure Tumor Associated Macrophages and to Predict Patient Response to Treatment

Resource links provided by NLM:


Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Measure tumor levels of irinotecan and SN-38 (in ng/mL) [ Time Frame: 12 months ]

Secondary Outcome Measures:
  • Safety profile of MM-398 in the presence of ferumoxytol (number and type of Adverse Events compared with histological control) [ Time Frame: 12 months ]
  • Tumor response Rate measured by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines [ Time Frame: 12 months ]
  • Half-life of the drug (t 1/2) in number of hours [ Time Frame: 12 months ]
    50% of total time of drug in plasma

  • Maximum concentration of drug in plasma (Cmax) in ng/mL [ Time Frame: 12 months ]
  • Measure of drug availability in the plasma (AUC) in ng/mL x hours [ Time Frame: 12 months ]
    Area under the plasma drug concentration versus time curve


Estimated Enrollment: 45
Study Start Date: November 2012
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pilot Phase: Ferumoxytol followed by MM-398 (CLOSED)
Ferumoxytol 5 mg/kg IV at the rate of 1 mL/sec, given once on Day 1. MM-398 80 mg/m2 IV over 90 min on Days 1 and 15 of every 4 week cycle
Drug: Ferumoxytol followed by MM-398
Ferumoxytol 5 mg/kg IV at 1mL/sec, given once. MM-398 80 mg/m2 IV over 90 min every 2 weeks, until progressive disease or intolerable toxicity
Experimental: Expansion Phase: Ferumoxytol followed by MM-398
Ferumoxytol 5 mg/kg IV at the rate of 1 mL/sec, given once on Day 1. MM-398 80 mg/m2 IV over 90 min on Days 1 and 15 of every 4 week cycle Cohort 1: ER and/or PR-positive BC Cohort 2: TNBC Cohort 3: BC with active brain metastasis
Drug: Ferumoxytol followed by MM-398
Ferumoxytol 5 mg/kg IV at 1mL/sec, given once. MM-398 80 mg/m2 IV over 90 min every 2 weeks, until progressive disease or intolerable toxicity

Detailed Description:

This study is conducted over two phases. The pilot phase of this trial is closed. The expansion phase of this trial is currently open to enrollment.

Pilot Phase: This study will enroll approximately 12 patients, up to 20 in total in the Pilot Phase and 30 patients in the Expansion Phase. The first three patients that are enrolled can have any solid tumor type; however subsequent patients must have NSCLC, CRC, TNBC, ER/PR positive breast cancer, pancreatic cancer, ovarian cancer, gastric cancer, gastro-oesophageal junction adenocarcinoma or head and neck cancer. No more than three patients with ER/PR positive breast cancer can be enrolled in the Pilot Phase and similar restrictions may be placed on other tumor types to ensure a heterogeneous population.

Expansion Phase: The expansion will enroll patients with advanced metastatic breast cancer into three cohorts:

Cohort 1: ER and/or PR-positive breast cancer Cohort 2: TNBC Cohort 3: BC with active brain metastasis

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed diagnosis of solid tumors, CRC, TNBC, ER/PR Breast Cancer, NSCLC, Pancreatic Cancer, Ovarian Cancer, Gastric Cancer, GEJ adenocarcinoma, Head and Neck Cancer
  • Metastatic disease
  • ECOG Performance Status 0 to 2
  • Adequate bone marrow, hepatic and renal function
  • Normal ECG
  • 18 years of age or above
  • Able to understand and sign informed consent

Expansion Phase Additional Criteria:

The following invasive breast cancer tumor sub-types are required:

  • Cohorts 1 and 2 must be documented to be HER2 negative as outlined in the ASCO/CAP 2013 guidelines for HER2 testing, defined by at least one of the following:

    • HER2 immunohistochemistry (IHC) staining of 0 or 1+,OR if HER2 IHC 2+
    • Negative by In-Situ Hybridization (ISH) based on defined as a Single probe average HER2 copy number <4.0 signals/cell
    • OR Negative by Dual-probe ISH defined as a HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell
  • Cohort 1: hormone receptor positive breast cancer patients with ER-positive and/or PR-positive tumors defined as ≥1% of tumor nuclei that are immunoreactive for ER and/or PR and HER2 negative
  • Cohort 2: triple negative breast cancer (TNBC) patients with ER-negative, PR-negative tumors defined as < 1% of tumor nuclei that are immunoreactive for ER and PR and HER2 negative
  • Cohort 3: Any sub-type of metastatic breast cancer and active brain metastases
  • Documented locally advanced or metastatic disease with at least two radiologically measurable lesions as defined by RECIST v1.1 (except Expansion Cohort 3)
  • ECOG performance status 0 or 1
  • Bone marrow reserves as evidenced by: ANC > 1,500 cells/μl without the use of hematopoietic growth factors; Platelet count > 100,000 cells/μl; Hemoglobin > 9 g/dL
  • Adequate hepatic function as evidenced by: Normal serum total bilirubin; AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN is acceptable if liver metastases are present)
  • Adequate renal function as evidenced by serum creatinine ≤ 1.5 x ULN
  • Normal ECG or ECG without any clinically significant findings
  • Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy
  • At least 18 years of age
  • Able to understand and sign an informed consent (or have a legal representative who is able to do so)
  • Received at least one cytotoxic therapy in the locally advanced and metastatic setting, with exception of TNBC patients who progressed within 12 months of adjuvant therapy
  • Received 5 prior lines of chemotherapy in the metastatic setting (no limit to prior lines of hormonal therapy in Cohort 1)
  • At least one lesion amenable to multiple pass core biopsy (exception: Cohort 3 patients)
  • Candidate for chemotherapy

Expansion Phase Cohort 3 additional inclusion criteria:

  • Radiographic evidence of new or progressive brain metastases after prior radiation therapy with at least one brain metastasis measuring ≥ 1 cm in longest diameter on gadolinium-enhanced MRI (note: progressive brain lesions are not required to meet RECIST criteria in order to be eligible; extra-cranial metastatic disease is also allowed)
  • Neurologically stable
  • No evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology. NOTE: discrete dural metastases are permitted.

Exclusion Criteria:

  • Active CNS metastasis (applies to pilot phase and expansion phase cohort 1 and 2 only)
  • Clinically significant GI disorders
  • Prior irinotecan or bevacizumab therapy within last 6 months and for Expansion Phase patients, have received any prior treatment with Topol inhibitor
  • Known hypersensitivity to MM-398 or ferumoxytol
  • Inability to undergo MRI
  • Active infection
  • Pregnant or breast feeding
  • Prior chemotherapy administered within 3 weeks, or within a time interval less than at least 5 half-lives of the agent, whichever is longer, prior to the first scheduled day of dosing in this study
  • Received radiation therapy in the last 14 days
  • Treated with parenteral iron in the previous 4 weeks
  Contacts and Locations
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): NCT01770353


Contacts
Contact: Ipsen Recruitment Enquiries clinical.trials@ipsen.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85159-5499
Contact: Clinical Trials Office All Mayo Clinic Locations    855-776-0015      
HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33607
United States, Michigan
University of Michighan Comprehensive Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
UNC- Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Navreet Dhindsa Ipsen
  More Information

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01770353     History of Changes
Other Study ID Numbers: MM-398-01-01-02
First Submitted: December 19, 2012
First Posted: January 17, 2013
Last Update Posted: October 3, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Ipsen:
solid tumors
Triple Negative Breast Cancer
Colorectal Cancer
ER/PR positive Breast Cancer
Pancreatic Cancer
Ovarian Cancer
Gastric Cancer
Head and Neck Cancer
MM-398
nanoliposomal irinotecan
Ferumoxytol
Gastro-Esophageal Junction Adenocarcinoma
TNBC

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Irinotecan
Camptothecin
Ferrosoferric Oxide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions