Clinical trial NCT01770353: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2013-01-17
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed 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

Eligibility 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

Primary outcomes:
measure: Pilot Phase: Tumour Levels of Irinotecan and SN-38 at Cycle 1 Day 4
timeFrame: At Cycle 1 Day 4 in the Pilot phase.
measure: Expansion Phase: Impact of the Quality of MRI Scan on Tumour Evaluation
timeFrame: Expansion phase Cycle 1: Pre FMX dose, 1-4 hours post FMX dose, 16-24 hours post FMX dose, 2 weeks Post FMX dose.
measure: Expansion Phase: Best Overall Tumour Response (BOR) by Tumour FMX Uptake Classification at 16 - 24 Hours Post-FMX Dose
timeFrame: 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:
measure: Pilot Phase + Expansion Phase: Median Progression-free Survival (PFS) (Non-CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Expansion Phase: Median PFS for Cohort 3 (CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Pilot Phase + Expansion Phase: BOR (Non-CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Expansion Phase: BOR for Cohort 3 (CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Pilot Phase + Expansion Phase: Objective Response Rate (ORR) (Non-CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Expansion Phase: ORR for Cohort 3 (CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Pilot Phase + Expansion Phase: Median Duration of Objective Response (DOR) (Non-CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Expansion Phase: Median DOR for Cohort 3 (CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Pilot Phase + Expansion Phase: Clinical Benefit Response (CBR) (Non-CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Expansion Phase: CBR for Cohort 3 (CNS Assessment)
timeFrame: Baseline and every 8 weeks from C1D1 until disease progression, unacceptable toxicity or withdrawal of consent.
measure: Pilot Phase + Expansion Phase: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs) Related to MM-398
timeFrame: From MM-398 treatment start up to 30 days after last dose.
measure: Pilot Phase: Time to Reach Maximum Plasma Concentration of Irinotecan and SN-38 (Tmax)
timeFrame: Pilot phase: C1D1 pre-MM-398 infusion, end of infusion, post-infusion (2, 72, 168 hours); C1D15 pre-infusion; 30 days follow-up visit.
measure: Expansion Phase: Irinotecan and SN-38 Tmax
timeFrame: Expansion phase: Cycles 1-3 pre-MM-398 infusion, end of infusion, post-infusion (2, 48,168 hours); D15 pre-infusion; 30 days follow-up visit.
measure: Pilot Phase: Maximum Observed Plasma Concentration of Irinotecan (Cmax)
timeFrame: Pilot phase: C1D1 pre-MM-398 infusion, end of infusion, post-infusion (2, 72, 168 hours); C1D15 pre-infusion; 30 days follow-up visit.
measure: Pilot Phase: SN-38 Cmax
timeFrame: Pilot phase: C1D1 pre-MM-398 infusion, end of infusion, post-infusion (2, 72, 168 hours); C1D15 pre-infusion; 30 days follow-up visit.
measure: Expansion Phase: Irinotecan Cmax
timeFrame: Expansion phase: Cycles 1-3 pre-MM-398 infusion, end of infusion, post-infusion (2, 48,168 hours); D15 pre-infusion; 30 days follow-up visit.
measure: Expansion Phase: SN-38 Cmax
timeFrame: Expansion phase: Cycles 1-3 pre-MM-398 infusion, end of infusion, post-infusion (2, 48,168 hours); D15 pre-infusion; 30 days follow-up visit.
measure: Pilot Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) for Irinotecan
timeFrame: Pilot phase: C1D1 pre-MM-398 infusion, end of infusion, post-infusion (2, 72, 168 hours); C1D15 pre-infusion; 30 days follow-up visit.
measure: Pilot Phase: SN-38 AUC(0-tlast)
timeFrame: Pilot phase: C1D1 pre-MM-398 infusion, end of infusion, post-infusion (2, 72, 168 hours); C1D15 pre-infusion; 30 days follow-up visit.
measure: Expansion Phase: Irinotecan AUC(0-tlast)
timeFrame: Expansion phase: Cycles 1-3 pre-MM-398 infusion, end of infusion, post-infusion (2, 48,168 hours); D15 pre-infusion; 30 days follow-up visit.
measure: Expansion Phase: SN-38 AUC(0-tlast)
timeFrame: Expansion phase: Cycles 1-3 pre-MM-398 infusion, end of infusion, post-infusion (2, 48,168 hours); D15 pre-infusion; 30 days follow-up visit.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michighan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: UNC- Lineberger Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.