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

NCT01770353 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MM-398-01-01-02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Pilot Phase: Tumour Levels of Irinotecan and SN-38 at Cycle 1 Day 4

  Two tumour biopsies were collected 72 hours after the first MM-398 IV infusion during Cycle 1 of the MM-398 Treatment phase of the Pilot phase for determination of tumour levels of irinotecan and SN-38 (an active metabolite). The lesions selected for biopsy were based on the results of the FMX-MRI obtained on Days 1, 2 and 4 of the FMX phase, and were collected from a previously non-biopsied lesion. The first core biopsy was taken in the region of the tumour that showed the greatest signal change on either the T2 or T1 sequences, based on FMX-MRI. The second core biopsy was taken from the region that showed the least signal change based on FMX-MRI, avoiding areas of necrosis.

  At Cycle 1 Day 4 in the Pilot phase.

• Expansion Phase: Impact of the Quality of MRI Scan on Tumour Evaluation

  Feasibility of FMX quantitation in tumour lesion was assessed through the acquisition of baseline (pre-FMX dose) and follow-up (post FMX dose) scans of sufficient quality to enable quantitative analysis to be performed. Quality was assessed by summarising scans as adequate for tumour evaluation or suboptimal but for which evaluation was completed for evaluation. Two FMX-MRI scans were taken on Day 1 (pre-FMX dosing) and on Day 2 (16-24 hours post dose) of the FMX phase. One MRI scan was also taken at 1-4 hours post FMX dose (Day 1 of FMX phase) and at 2 weeks post FMX dose (Day 15 of the MM-398 phase). It was possible for a subject to have 2 FMX-MRI scans for the same visit and timepoint corresponding to a scan target location. The number of MRI scan results that were assessed to be adequate or suboptimal at each timepoint are presented.

  Expansion phase Cycle 1: Pre FMX dose, 1-4 hours post FMX dose, 16-24 hours post FMX dose, 2 weeks Post FMX dose.

• Expansion Phase: Best Overall Tumour Response (BOR) by Tumour FMX Uptake Classification at 16 - 24 Hours Post-FMX Dose

  FMX tumour uptake was classified as 'low tumour uptake' or 'high tumour uptake', and was determined for 16 to 24-hours post-FMX dosing. The FMX uptake in a subject's lesions was classified using the median of the baseline-corrected FMX values at that timepoint across all subjects. The best radiological overall tumour response to MM-398 from the beginning to the end of the study was assessed using both the Investigator and imaging results per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (Non-central nervous system \[CNS\] assessments; Cohorts 1, 2 and 3). Tumour response was classified as a Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). BOR is presented by tumour uptake classification at 16-24 hours post-FMX dose by cohort for the non-CNS RECIST assessment.

  Expansion phase: C1D2 FMX phase, and every 8 weeks for RECIST assessments from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

Secondary Outcomes (21)

• Pilot Phase + Expansion Phase: Median Progression-free Survival (PFS) (Non-CNS Assessment)

  Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

• Expansion Phase: Median PFS for Cohort 3 (CNS Assessment)

  Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

• Pilot Phase + Expansion Phase: BOR (Non-CNS Assessment)

  Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

• Expansion Phase: BOR for Cohort 3 (CNS Assessment)

  Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

• Pilot Phase + Expansion Phase: Objective Response Rate (ORR) (Non-CNS Assessment)

  Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.

Study Arms (2)

Pilot Phase: Ferumoxytol followed by MM-398

EXPERIMENTAL

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; Drug: MM-398

Expansion Phase: Ferumoxytol followed by MM-398

EXPERIMENTAL

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; Drug: MM-398

Interventions

Ferumoxytol DRUG

Ferumoxytol 5 mg/kg IV as a single bolus injection, given once.

Expansion Phase: Ferumoxytol followed by MM-398; Pilot Phase: Ferumoxytol followed by MM-398

MM-398 DRUG

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

Expansion Phase: Ferumoxytol followed by MM-398; Pilot Phase: Ferumoxytol followed by MM-398

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (7)

Mayo Clinic

Scottsdale, Arizona, 85159-5499, United States

Location

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33607, United States

Location

University of Michighan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

UNC- Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (2)

• Ravi H, Arias-Lorza AM, Costello JR, Han HS, Jeong DK, Klinz SG, Sachdev JC, Korn RL, Raghunand N. Pretherapy Ferumoxytol-enhanced MRI to Predict Response to Liposomal Irinotecan in Metastatic Breast Cancer. Radiol Imaging Cancer. 2023 Mar;5(2):e220022. doi: 10.1148/rycan.220022.

  PMID: 36734848 DERIVED

• Sachdev JC, Munster P, Northfelt DW, Han HS, Ma C, Maxwell F, Wang T, Belanger B, Zhang B, Moore Y, Thiagalingam A, Anders C. Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase. Breast Cancer Res Treat. 2021 Feb;185(3):759-771. doi: 10.1007/s10549-020-05995-7. Epub 2020 Nov 17.

  PMID: 33201358 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Stomach Neoplasms; Head and Neck Neoplasms

Interventions

Ferrosoferric Oxide; irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Stomach Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Limitations and Caveats

Data for the subjects in the 3 Expansion Phase cohorts were combined when presenting results for the overall Expansion Phase because all cohorts were defined in the protocol to contain subjects with BC.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen Bioscience, Inc

clinical.trials@ipsen.com

See email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: January 17, 2013
• Study Start: November 1, 2012
• Primary Completion: October 2, 2018
• Study Completion: October 2, 2018
• Last Updated: November 27, 2019
• Results First Posted: October 28, 2019

Record last verified: 2019-11

Locations

US (7)