Clinical Trials /

Merestinib on Bone Metastases in Subjects With Breast Cancer

NCT03292536

Description:

This is an open label, pharmacodynamics, intrapatient dose escalation phase 1B study.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Merestinib on Bone Metastases in Subjects With Breast Cancer
  • Official Title: An Exploratory Phase 1B Study to Assess the Effects of Merestinib on Bone Metastases in Subjects With Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: HCI103657
  • NCT ID: NCT03292536

Conditions

  • Bone Metastases
  • Breast Cancer

Interventions

DrugSynonymsArms
MerestinibMerestinib, all patients

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Merestinib, all patientsExperimental
  • Merestinib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events that Occur
Time Frame:12 weeks, checked at every visit in that time period
Safety Issue:
Description:To assess the tolerability of merestinib in combination with standard breast cancer therapies.

Secondary Outcome Measures

Measure:Absolute and percentage change in serum B-CTX, TRAP-5b, P1NP and BSAP
Time Frame:12 weeks
Safety Issue:
Description:To measure the absolute and percentage change in serum β-CTX, TRAP-5b, P1NP, and BSAP at time points from baseline to 12 weeks.
Measure:Time to skeletal-related events
Time Frame:12 weeks
Safety Issue:
Description:To evaluate determine time to skeletal-related event(s) following initiation of merestinib dosing
Measure:Change in pain scores
Time Frame:12 weeks
Safety Issue:
Description:To evaluate change in pain as measured by pain scores during and after 12 weeks of merestinib treatment
Measure:Change in pain by narcotic use
Time Frame:12 weeks
Safety Issue:
Description:To evaluate change in pain as measured by narcotic use) during and after 12 weeks of merestinib treatment
Measure:Change in bone lesion uptake
Time Frame:12 weeks
Safety Issue:
Description:To evaluate the change in bone lesion uptake on NaF PET scan after 12 weeks of merestinib treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

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