Clinical Trials /

Pharmacokinetic and Safety Study of MRX-2843 in Adults With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors

NCT03510104

Description:

This first-in-human open-label, dose escalation study is designed to evaluate the safety, tolerability, and PK of MRX-2843 in subjects with relapsed/refractory advanced and/or metastatic solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pharmacokinetic and Safety Study of MRX-2843 in Adults With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors
  • Official Title: A Phase I Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of MRX-2843 in Adult Subjects With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2843-1001
  • NCT ID: NCT03510104

Conditions

  • Advanced Cancer
  • Metastatic Cancer
  • Neoplasms
  • Neoplasm Metastasis
  • Neoplastic Processes
  • Pathologic Processes

Interventions

DrugSynonymsArms
MRX-2843MRX-2843

Purpose

This first-in-human open-label, dose escalation study is designed to evaluate the safety, tolerability, and PK of MRX-2843 in subjects with relapsed/refractory advanced and/or metastatic solid tumors.

Trial Arms

NameTypeDescriptionInterventions
MRX-2843ExperimentalMRX-2843: Dose Escalation Successive dose escalation cohorts to determine MTD
  • MRX-2843

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female at least 18 years of age.

          -  Histologically or cytologically confirmed, measurable (defined as those that could be
             accurately measured in a least 1 dimension with a longest diameter ≥20 mm using
             conventional techniques or ≥10 mm with spiral computed tomography scan) or evaluable
             solid malignancy (with the exception of primary central nervous system [CNS] tumors)
             per RECIST 1.1. Scans performed within 1 month of starting study drug will be
             accepted.

          -  Received at least one systemic therapy for advanced disease, with no further approved
             treatment options that provide proven clinical benefit.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

          -  Females of childbearing potential who are sexually active with a nonsterilized male
             partner agree to use 2 methods of effective contraception from screening, and agree to
             continue using such precautions for 90 days after the final dose of study drug;
             cessation of birth control after this point should be discussed with a responsible
             physician. Periodic abstinence, the rhythm method, and the withdrawal method are not
             acceptable methods of birth control.

          -  Nonsterilized males who are sexually active with a female of childbearing potential
             must agree to use an acceptable method of effective contraception from Day 1 and for
             90 days after the final dose of study drug.

          -  Female subjects of childbearing potential must be nonpregnant, nonlactating, and have
             a negative pregnancy test result at Screening and Day 1 of Cycles 1-6.

          -  Able to provide written, informed consent before initiation of any study related
             procedures, and is able, in the opinion of the Investigator, to comply with all the
             requirements of the study.

          -  Able to swallow oral medication.

          -  Subject has the following laboratory values at Screening:

               1. Absolute neutrophil count ≥1500/mm3

               2. Platelet count ≥100,000/mm3

               3. Hemoglobin ≥9.0 g/dL (must be >2 weeks post-red blood cell transfusion)

               4. Bilirubin ≤1.5x the upper limit of normal (ULN). For subjects with documented
                  Gilbert's disease, bilirubin ≤3.0 mg/dL. For subjects with documented liver
                  metastases, bilirubin ≤ 2.5x ULN.

               5. Serum creatinine ≤1.5x the ULN or creatinine clearance (CrCl) ≥50 mL/min.

               6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x the ULN
                  (≤5x the ULN for subjects with liver metastases)

        Exclusion Criteria:

          -  Subject has an abnormal electrocardiogram (ECG) that, in the Investigator's opinion,
             is clinically significant and would preclude study participation.

          -  Subject has QT interval corrected (QTc) >480 ms (both males and females) at Screening
             (repeat values may be obtained during the period between Screening and admission to
             the study site).

          -  Subject has any surgical or medical condition (active or chronic) that may interfere
             with drug absorption, distribution, metabolism, or excretion of the study drug, or any
             other condition that may place the subject at risk for such interference (for example,
             short bowel syndrome or inflammatory bowel disease).

          -  Subject has a history of Type 1 Diabetes (T1D) or is considered at high risk for T1D,
             where high risk is defined as

               1. Subject has 1 first-degree relative (FDR; defined as parents, offspring or
                  siblings) with T1D AND A1C value > 6.5% or

               2. Subject has 2+FDR with T1D

          -  Subject has uncontrolled hypertension, defined as a blood pressure reading >160/100
             mmHg, despite maximum antihypertensive therapy.

          -  Subject has received:

               1. Radionuclide treatment within 6 weeks of the first dose of study drug in this
                  study

               2. Local palliative radiation therapy (XRT) (small port) ≤2 weeks before first dose
                  of study drug

               3. Treatment with therapeutic doses of metaiodobenzylguanidine (MIBG) ≤6 weeks
                  before first dose of study drug

               4. Prior total body irradiation, total craniospinal XRT, or ≥50% radiation of pelvis
                  within 6 months of receiving first dose of study drug

               5. Treatment with a monoclonal antibody within 28 days or 5 half-lives, whichever is
                  shorter, from treatment with first dose of study drug

               6. Therapy with a growth factor within 7 days of starting study drug

               7. Chemotherapy within 3 weeks of starting study drug (6 weeks if prior nitrosourea)

               8. Subjects receiving systemic (oral or parenteral) corticosteroid therapy within 7
                  days of first dose of study drug or a requirement for chronic systemic
                  immunosuppressive therapy for any reason. Topical or inhaled steroids are
                  allowed.

          -  Subject has not fully recovered to baseline or National Cancer Institute Common
             Terminology Criteria for Adverse Events (NCI-CTCAE) ≤ Grade 1 from toxicity due to all
             prior therapies, except alopecia and other non-clinically significant AEs.

          -  Subject has any history of human immunodeficiency virus (HIV) or immunodeficiency at
             Screening.

          -  Subject has a diagnosis of chronic active hepatitis B or C.

          -  Subject has uncontrolled intercurrent illness including, but not limited to ongoing or
             active bacterial, fungal, or viral infection requiring intravenous therapy (not
             prophylaxis) at the time of study enrollment, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Subject has a history of a major adverse cardiac event, including cerebrovascular
             accident or myocardial infarction within the prior 6 months, or uncontrolled
             congestive heart failure (New York Heart Association class 3 or 4) at Screening.

          -  Subject has active, suspected, or previously documented autoimmune disease, defined as
             requiring systemic treatment.

          -  Subject has known or suspected history of retinitis pigmentosa or known or suspected
             familial history of retinitis pigmentosa.

          -  Subject has prothrombin time/International Normalized Ratio or partial thromboplastin
             time test results at screening ≥1.5 x ULN.

          -  Subject requires concomitant treatment, in therapeutic doses, with anticoagulants such
             as warfarin-related agents, thrombin or FXa inhibitors, or antiplatelet agents (eg,
             clopidogrel). Low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1 mg/day), and
             prophylactic low molecular weight heparin are permitted.

          -  Subject had surgery (excluding line insertions) within 1 month of the first dose of
             study drug or has lingering wound complications.

          -  Subject is unable or unwilling to abide by the study protocol or cooperate fully with
             the Investigator or designee.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects with Dose Limiting Toxicities (DLTs)
Time Frame:Baseline to the end of Cycle 1 (up to 28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Determine Maximum Tolerated Dose (MTD) in mg of MRX-2843
Time Frame:Baseline to end of Cycle 1 (up to 28 days)
Safety Issue:
Description:
Measure:AUC0-t: area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (t)
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:AUC0-inf: area under the concentration-time curve from time 0 to infinity
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:AUC0-τ: area under the concentration-time curve from time 0 to tau, where tau is the dosing interval
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:Cmax: maximum observed plasma concentration
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:Tmax: time to reach maximum observed plasma concentration
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:λz: terminal phase elimination rate constant
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:t1/2: apparent terminal elimination half-life
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:CL/F: apparent total body clearance
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:
Measure:Vz/F: apparent volume of distribution of the terminal phase
Time Frame:Day 1 and Day 16 of Cycle 1
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Meryx, Inc.

Trial Keywords

  • MerTK

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