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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

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ClinicalTrials.gov Identifier: NCT01770353
Recruitment Status : Active, not recruiting
First Posted : January 17, 2013
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Ipsen

Brief Summary:
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 or disease Intervention/treatment Phase
Solid Tumors ER/PR Positive Breast Cancer Triple Negative Breast Cancer Metastatic Breast Cancer With Active Brain Metastasis Drug: Ferumoxytol Drug: MM-398 Phase 1

Detailed Description:

This study is conducted over two phases. The pilot phase of this trial is closed. The expansion phase of this trial has completed enrolment, patients are still ongoing.

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 in the Pilot Phase can have any solid tumor type; however subsequent patients must have Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Triple negative breast cancer (TNBC), Estrogen Receptor/Progesterone Receptor (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 of 10 patients each depending on sub-type of breast cancer:

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
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
Study Start Date : November 2012
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018


Arm Intervention/treatment
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 IV over 90 min on Days 1 and 15 of every 4 week cycle
Drug: Ferumoxytol
Ferumoxytol 5 mg/kg IV at 1mL/sec, given once.

Drug: MM-398
MM-398 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 IV over 90 min dose 1 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
Ferumoxytol 5 mg/kg IV at 1mL/sec, given once.

Drug: MM-398
MM-398 IV over 90 min every 2 weeks, until progressive disease or intolerable toxicity




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

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

  4. Maximum concentration of drug in plasma (Cmax) in ng/mL [ Time Frame: 12 months ]
  5. 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

  6. Best Overall Response (BOR) [ Time Frame: 12 months ]
    the best response as recorded from the start of MM-398 until disease progression

  7. Objective Response Rate (ORR) [ Time Frame: 12 months ]
    the proportion of patients with a BOR characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.

  8. Clinical benefit rate [ Time Frame: 12 months ]
    the proportion of patients with a BOR characterized as a CR, PR, or Stable Disease (SD) ≥ 24 weeks.

  9. Duration of Response (DR) [ Time Frame: 12 months ]
    the time from first documentation of response (CR or PR whichever occurs first) to the date of disease progression or to death due to any cause, whichever occurs first.

  10. Progression-free survival (PFS) [ Time Frame: 12 months ]
    the time from first dose of MM-398 to the date of radiologic disease progression per Investigator or death due to any cause, whichever occurs first.



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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:

All subjects:

  • Pathologically confirmed diagnosis of solid tumors
  • Metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
  • Adequate bone marrow, hepatic and renal function
  • Normal Electrocardiogram (ECG)
  • 18 years of age or above
  • Able to understand and sign informed consent

Pilot study only:

- CRC, TNBC, ER/PR Breast Cancer, NSCLC, Pancreatic Cancer, Ovarian Cancer, Gastric Cancer, Gastroesophageal Junction (GEJ) adenocarcinoma, Head and Neck Cancer

Expansion Phase Additional Criteria:

  • Locally advanced or metastatic breast cancer
  • Received at least one cytotoxic therapy in the locally advanced and metastatic setting
  • Received ≤ 5 prior lines of chemotherapy in the metastatic setting
  • Candidate for chemotherapy

Expansion Phase Cohort 3 additional inclusion criteria:

  • Breast cancer with active brain metastasis
  • Neurologically stable

Exclusion Criteria:

  • Active Central nervous system (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

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


Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85159-5499
HonorHealth
Scottsdale, Arizona, United States, 85258
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33607
United States, Michigan
University of Michighan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, North Carolina
UNC- Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Medical Director Ipsen

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01770353     History of Changes
Other Study ID Numbers: MM-398-01-01-02
First Posted: January 17, 2013    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

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

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