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

Ipsen

Status and phase: Completed; Phase 1

Conditions: ER/PR Positive Breast Cancer; Metastatic Breast Cancer With Active Brain Metastasis; Triple Negative Breast Cancer; Solid Tumors

Treatments: Drug: MM-398; Drug: Ferumoxytol

Study type: Interventional

Funder types: Industry

Identifiers

NCT01770353

MM-398-01-01-02

Details and patient eligibility

About

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.

Full description

This study is conducted over two phases.

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

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

45 participants in 2 patient groups

Pilot Phase: Ferumoxytol followed by MM-398

Experimental group

Description:

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

Treatment:

Drug: Ferumoxytol

Drug: MM-398

Expansion Phase: Ferumoxytol followed by MM-398

Experimental group

Description:

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

Treatment:

Drug: Ferumoxytol

Drug: MM-398