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

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 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 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 and to Predict Patient Response to Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Ferumoxytol

Genetic and Rare Diseases Information Center resources: Ovarian Cancer Pancreatic Cancer Stomach Cancer

U.S. FDA Resources

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:	October 2017
Estimated Primary Completion Date:	June 2017 (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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
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: Istvan Molnar, MD	617-441-1000 ext 7649	imolnar@merrimack.com

Locations


United States, Arizona
Mayo Clinic	Not yet 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

Merrimack Pharmaceuticals

Investigators


Study Director:	Istvan Molnar, MD	Merrimack Pharmaceuticals

More Information


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:	July 7, 2016
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 TNBC

Additional relevant MeSH terms:


Breast Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases	Skin Diseases Ferrosoferric Oxide Hematinics Parenteral Nutrition Solutions Pharmaceutical Solutions

ClinicalTrials.gov processed this record on September 27, 2016