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Merestinib on Bone Metastases in Subjects With Breast Cancer

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ClinicalTrials.gov Identifier: NCT03292536
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : December 5, 2018
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
University of Utah

Brief Summary:
This is a single arm, open label, pharmacodynamics, intrapatient dose escalation phase 1B study.

Condition or disease Intervention/treatment Phase
Bone Metastases Breast Cancer Drug: Merestinib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Intervention Model Description: a single arm, open label, pharmacodynamics, intrapatient dose escalation phase 1B study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Exploratory Phase 1B Study to Assess the Effects of Merestinib on Bone Metastases in Subjects With Breast Cancer
Actual Study Start Date : January 11, 2018
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Merestinib, all patients Drug: Merestinib

*The merestinib does escalation timing will depend on the schedule of the other anticancer regimen*

Subjects will receive merestinib 40mg PO Qday (dose level 1) for 2 to 4 weeks followed by 80mg PO daily (dose level 2) for 4 to 10 weeks





Primary Outcome Measures :
  1. Adverse Events that Occur [ Time Frame: 12 weeks, checked at every visit in that time period ]
    To assess the tolerability of merestinib in combination with standard breast cancer therapies.

  2. Change in urinary N-telopeptide level [ Time Frame: 12 weeks ]
    To measure the change in urinary N-telopeptide level after 12 weeks of therapy with merestinib


Secondary Outcome Measures :
  1. Absolute and percentage change in serum B-CTX, TRAP-5b, P1NP and BSAP [ Time Frame: 12 weeks ]
    To measure the absolute and percentage change in serum β-CTX, TRAP-5b, P1NP, and BSAP at time points from baseline to 12 weeks.

  2. Time to skeletal-related events [ Time Frame: 12 weeks ]
    To evaluate determine time to skeletal-related event(s) following initiation of merestinib dosing

  3. Change in pain scores [ Time Frame: 12 weeks ]
    To evaluate change in pain as measured by pain scores during and after 12 weeks of merestinib treatment

  4. Change in pain by narcotic use [ Time Frame: 12 weeks ]
    To evaluate change in pain as measured by narcotic use) during and after 12 weeks of merestinib treatment

  5. Change in bone lesion uptake [ Time Frame: 12 weeks ]
    To evaluate the change in bone lesion uptake on NaF PET scan after 12 weeks of merestinib treatment



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 1 bone metastases must be present
  • Urinary N-telopeptide level above 20nM BCE/mM creatinine measured at ARUP
  • Archived or freshly biopsied primary and/or bone metastatic tumor tissue available in paraffin-embedded blocks or slides that is expected to yield 9 slides
  • Life expectancy of ≥ 6 months
  • Toxicity related to prior treatments must either have resolved to grade 1 or less, returned to baseline, or be deemed irreversible
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 28 days prior to enrollment)
  • Planning to remain on current breast cancer therapy for at least 12 weeks.
  • At least one prior line of therapy for metastatic breast cancer
  • Concurrent treatment with bisphosphonates or denosumab is required.

Exclusion Criteria:

  • Unable to swallow or take anything orally
  • ECG abnormalities:

    • Prolonged QTc (Bazette's or Fredericia's correction) interval on screening ECG (≥ 450 msec)
    • QRS ˃ 120 msec
    • PR ˃ 210 msec
    • Any prior history, or current evidence of second- or third-degree heart block
    • Heart rate ˂ 40 beats per minute at screening
    • ECG second degree heart block (Mobitz's Type 2 or Wenckebach)
    • Complete heart block
    • Left bundle branch block or bifascicular block (right bundle branch block and left anterior hemiblock together)
    • Episodes of ventricular tachycardia
  • Any known prior malignancy (not including non-melanoma skin cancers), unless treated with curative intent
  • A serious uncontrolled medical disorder or active infection, which would impair the ability of the subject to receive protocol therapy
  • Current or recent (within 3 months) gastrointestinal disease that could impact the absorption (i.e., unmanageable diarrhea or malabsorption at the time of screening)
  • Inadequate bone marrow function defined as:

    • Absolute neutrophil count (ANC) ˂ 1,500 cells/mm3
    • Platelet count ˂ 100,000 cells/mm3
    • Hemoglobin ˂ 9 g/dL
  • Inadequate hepatic function defined as:

    • Total bilirubin ˃ 1.5 x institutional upper limit of normal (IULN) (Unless due to diagnosis of Gilbert's Syndrome)
    • Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) ˃ 2.5 x IULN
  • Inadequate renal function defined as: Serum creatinine ˃ 1.5 x ULN
  • Prothrombin time (PT)/partial thromboplastin time (PTT) ˃ 1.5 times the ULN
  • Serum sodium, potassium, and calcium levels equivalent to Grade 1 AE values as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Any atrophic macular condition including intermediate or advanced age-related macular degeneration
  • Patients receiving medications that are known to be substrates of CYP2C8 (including paclitaxel), CYP2C9, or CYP2C19 or to be oral substrates of CYP3A with narrow therapeutic window (listed on http://medicine.iupui.edu/clinpharm/ddis/main-table). Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of merestinib
  • Exposure to any investigational drug or placebo within 4 weeks of enrollment
  • Any other sound medical, psychiatric, and/or social reasons as determined by the investigator
  • History of diseases with influence on bone metabolism, such as Paget's disease, osteogenesis imperfecta, active primary or secondary hyperparathyroidism, and primary or secondary hyperthyroidism within 12 months prior to study entry
  • Patients with known symptomatic brain metastasis. Subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment and no neurological signs or symptoms) will be allowed
  • History of allergy to merestinib or chemically related compounds
  • History of osteonecrosis of the jaw
  • Change in chemotherapy or hormone therapy within 8 weeks of the start of the study.
  • Active gout or inflammatory arthritis requiring treatment
  • Use within 28 days of registration of calcitonin, recombinant parathyroid hormone-related peptides, mithramycin, radium, strontium ranelate, or gallium nitrate.
  • Adult patients who require monitored anesthesia for PET scanning due to claustrophobia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03292536


Contacts
Contact: Janna Espinosa 801-585-0571 Janna.Espinosa@hci.utah.edu

Locations
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Janna Espinosa    801-585-0571    Janna.Espinosa@hci.utah.edu   
Principal Investigator: Adam Cohen, MD         
Sponsors and Collaborators
University of Utah
Eli Lilly and Company

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT03292536     History of Changes
Other Study ID Numbers: HCI103657
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases