Pilot Study to Determine Biodistribution of MM-398 and Feasibility of Ferumoxytol as a Tumor Imaging Agent

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Merrimack Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01770353
First received: December 19, 2012
Last updated: May 5, 2015
Last verified: May 2015
  Purpose

This is a Phase I Pilot 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
Triple Negative Breast Cancer
ER/PR Positive 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
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Pilot Study in Patients Treated With MM-398 to Determine Tumor Drug Levels and to Evaluate the Feasibility of Ferumoxytol Magnetic Resonance Imaging to Measure Tumor Associated Macrophages

Resource links provided by NLM:


Further study details as provided by Merrimack Pharmaceuticals:

Primary Outcome Measures:
  • Measure tumor levels of irinotecan and SN-38 (in ng/mL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • Tumor response Rate measured by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Half-life of the drug (t 1/2) in number of hours [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    50% of total time of drug in plasma

  • Maximum concentration of drug in plasma (Cmax) in ng/mL [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Measure of drug availability in the plasma (AUC) in ng/mL x hours [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Area under the plasma drug concentration versus time curve


Estimated Enrollment: 45
Study Start Date: November 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: January 2016 (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 weekly 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 weekly cycle Cohort 1: ER and/or PR-positive breast cancer 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 cohorts of single indications of patients with metastatic breast cancer in 3 cohorts:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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:

  • 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 metastatic disease with at least two radiologically measurable lesions as defined by RECIST v1.1 (except Cohort 3, see inclusion criterion o below)
  • Received at least one cytotoxic therapy in the metastatic setting, with exception of TNBC patients who progressed within 12 months of adjuvant therapy
  • Received ≤ 3 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)

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)

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
  • Known hypersensitivity to MM-398 or ferumoxytol
  • Inability to undergo MRI
  • Active infection
  • Pregnant or breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01770353

Contacts
Contact: Eliel Bayever, MD 617-441-1000 ebayever@merrimackpharma.com

Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States
Sponsors and Collaborators
Merrimack Pharmaceuticals
Investigators
Study Director: Eliel Bayever, MD Merrimack Pharmaceuticals
  More Information

No publications provided

Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01770353     History of Changes
Other Study ID Numbers: MM-398-01-01-02
Study First Received: December 19, 2012
Last Updated: May 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Merrimack Pharmaceuticals:
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

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Ferrosoferric Oxide
Hematinics
Hematologic Agents
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2015