Clinical Trial 18205

Cancer Type: Breast
Interventions:Ferumoxytol; MM-398

Study Type: Treatment
Phase of Study: Pilot
Investigators:


    Overview

    Study Title

    A 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

    Summary

    The primary purpose of this study is to see if the study drug known as MM-398, has an effect on these types of cancer, and if ferumoxytol MRI (Fe-MRI) can be used in participancts taking MM-398 to predict MM-398 activity.

    Objective

    3.1 PRIMARY OBJECTIVES Pilot Phase: In patients with NSCLC, CRC, TNBC, ER/PR positive breast cancer, pancreatic cancer, ovarian cancer, gastric cancer, GEJ adenocarcinoma or head and neck cancer, who are undergoing therapy with MM-398: *To evaluate the feasibility of delayed ferumoxytol MRI (Fe-MRI) to identify tumor associated macrophages (TAMs). * To measure tumor levels of irinotecan and SN-38. Expansion Phase: In patients with metastatic breast cancer: * To further investigate the feasibility of ferumoxytol (FMX) quantitation in tumor lesions. * To characterize the relationship between ferumoxytol (FMX) tumor uptake and tumor response to MM-398. 3.2 SECONDARY OBJECTIVES Pilot Phase: * To estimate the correlations between Fe-MRI, TAM levels, and tumor levels of irinotecan and SN-38 with administration of MM-398. * To determine the value of Fe-MRI in directing tissue biopsy. All Phases: * To characterize the safety profile of MM-398 in the presence of FMX. * To assess tumor response. * To characterize the pharmacokinetics (PK) of MM-398. Expansion Phase: * To characterize the efficacy of MM-398 in patients with metastatic breast cancer using key efficacy indicators such as objective response rate and clinical benefit rate. * To further characterize the safety profile of MM-398, in the presence of FMX, in metastatic breast cancer patients. * To assess the analytical performance of Fe-MRI measurements and optimize Fe-MRI parameterization. 3.3 EXPLORATORY OBJECTIVES Pilot Phase: * To estimate the correlations between potential pharmacodynamic (PD) markers (Fe-MRI, TAM, tumor irinotecan, tumor SN-38 levels) and safety. * To estimate the correlations between potential PD markers (Fe-MRI, TAM, tumor irinotecan,tumor SN-38 levels) and tumor response.

    Inclusion Criteria

  • ALL PHASES:
  • Pathologically confirmed solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
  • Pilot Phase (Completed)
  • Expansion Phase: the following invasive breast cancer tumor sub-types are required: Cohorts 1 and 2 must be documented to be HER2 negative as outlined in the ASCO/CAP 2013 guidelines for HER2 testing. In addition, breast cancer patients must patients must be * 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 less than 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 1 radiologically measurable lesion as defined by RECIST v1.1 (except Cohort 3)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Adequate bone marrow, hepatic and renal function
  • Normal (or without clinically significant findings) electrocardiogram (ECG)
  • 18 years of age or above
  • Able to understand and sign informed consent
  • EXPANSION PHASE ADDITIONAL CRITERIA:
  • Received at least one cytotoxic therapy in the metastatic setting, with exception of TNBC patients who progressed within 12 months of adjuvant therapy
  • Received 5 or less prior lines of chemotherapy in the metastatic setting (no limit to prior lines of hormonal therapy in Cohort 1)
  • Candidate for chemotherapy
  • At least one lesion amenable to multiple pass core biopsy (exception: Cohort 3 participants).
  • EXPANSION PHASE COHORT 3 ADDITIONAL 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 magnetic resonance imaging (MRI) (note: progressive brain lesions are not required to meet Response Evaluation Criteria in Solid Tumors (RECIST) in order to be eligible; extra-cranial metastatic disease is also allowed).
  • 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)
  • Imaging following prior radiation is not consistent with pseudo-progression in the judgment of treating clinician
  • Neurologically stable
  • No evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology-NOTE: discrete dural metastases are permitted.

  • Exclusion Criteria

  • Active central nervous system metastases, indicated by clinical symptoms, cerebral edema, or steroid requirement (applies to Pilot Phase and Expansion Phase Cohorts 1-2 only)
  • Clinically significant gastrointestinal (GI) disorders
  • Prior irinotecan or bevacizumab (or other anti-VEGF therapy) within the last six months; and for Expansion Phase patients, have received any prior treatment with a Topo1 inhibitor (irinotecan-derived or topotecan)
  • History of any second malignancy in the last 3 years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years.
  • Inability to undergo MRI
  • History of allergic reactions to compounds similar to ferumoxytol as described in full prescribing information for ferumoxytol injection, or to other IV iron replacement products (e.g., parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)
  • Documented history of allergies to multiple drugs
  • Known hypersensitivity to any of the components of MM-398, or other liposomal products
  • Active infection
  • Pregnant or breast feeding
  • Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease
  • 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
  • Evidence of Iron overload
  • Treated with parenteral iron in the previous 4 weeks
  • HIV-positive patients on combination antiretroviral therapy or other conditions requiring treatment where there is a potential for ferumoxytol to have negative pharmacokinetic interactions