Clinical Trials /

A Study of OKI-179 in Patients With Solid Tumors

NCT03931681

Description:

This study is a Phase 1, single center, open-label study, assessing single agent dose escalation of OKI-179.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of OKI-179 in Patients With Solid Tumors
  • Official Title: A Phase 1 Study of OKI-179 as a Single Agent in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: OKI-179-101
  • NCT ID: NCT03931681

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
OKI-179Experimental: Phase 1 - Dose Escalation

Purpose

This study is a Phase 1, single center, open-label study, assessing single agent dose escalation of OKI-179.

Trial Arms

NameTypeDescriptionInterventions
Experimental: Phase 1 - Dose EscalationExperimentalThis is a single arm, dose escalation trial evaluating OKI-179 given orally on a daily basis. Patients will take OKI-179 orally (PO) on Days 1 - 4, 8 - 11 and 15 - 18 in 21-day cycles (± 3 days), under fasted conditions. The design is a modified 3+3 design to determine the maximum tolerated dose. There is no comparative arm.
  • OKI-179

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all of the following criteria to be eligible for enrollment.

          -  Histologically or cytologically confirmed solid tumors, advanced or metastatic
             disease, refractory to standard therapy or for whom no standard therapy exists, or the
             patient is ineligible for standard therapy(ies).

          -  At least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumor
             (RECIST) version 1.1.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 within 14 days
             prior to Cycle 1 Day 1.

          -  Signed informed consent prior to initiation of any study-related procedures that are
             not considered standard of care.

          -  Male or female, ≥ 18 years of age at time of signing consent.

          -  Adequate hematologic and organ function as defined by the following criteria within 14
             days prior to Cycle 1 Day 1:

          -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; excluding measurements obtained within
             7 days after daily administration of filgrastim/sargramostim or within 3 weeks after
             administration of pegfilgrastim.

          -  Platelet count ≥ 100 × 109/L; excluding measurements obtained within 3 days after
             transfusion of platelets.

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper
             limits of normal (ULN); if liver function abnormalities are due to underlying liver
             metastases, AST and ALT ≤ 5 × ULN.

          -  Total serum bilirubin ≤ 1.5 × ULN, or ≤ 3 × ULN if attributed to Gilbert's Syndrome.

          -  Serum creatinine ≤ 1.5 x ULN or Creatinine clearance (CrCl) ≥ 50 mL/min; the CrCl can
             be measured from urine or calculated from serum creatinine (Cockcroft‑Gault Equation).

          -  Female patients of childbearing potential must have a negative serum beta-human
             chorionic gonadotropin (β-hCG) test within 14 days prior to Cycle 1 Day 1.

          -  Male patients and female patients of childbearing potential must agree to use an
             effective method of contraception per institutional standard prior to the first dose
             and for 90 days after the last dose of OKI-179.

          -  Willingness and ability to comply with all scheduled visits, treatment plan,
             laboratory tests and other study procedures.

        Exclusion Criteria:

        Patients meeting any of the following criteria are ineligible for enrollment in the study:

          -  Any of the following treatment interventions within the specified time frame prior to
             Cycle 1 Day 1:

          -  Major surgery within 28 days (the surgical incision should be fully healed prior to
             study drug administration).

          -  Radiation therapy within 21 days; however, if the radiation portal covered ≤ 5% of the
             bone marrow reserve, the patient is eligible irrespective of the end date of
             radiotherapy. None of the recently irradiated lesions can be included in the
             measurable disease assessment.

          -  Cytotoxic therapy within 21 days (nitrosoureas or mitomycin within 42 days,
             capecitabine within 14 days).

          -  Monoclonal antibodies within 28 days.

          -  Current use of an investigational agent that is not expected to be cleared by Cycle 1
             Day 1 or that has demonstrated to have prolonged/late side effects.

          -  Continuation of luteinizing hormone-releasing hormone (LHRH) agonists for prostate
             cancer, bisphosphonates for bone disease, denosumab for bone metastases and
             corticosteroids are permitted provided the dose does not change during the study.

          -  Side effects from prior treatment interventions not resolved to a Grade ≤ 1 (except
             alopecia or peripheral neuropathy).

          -  Prior Histone deacetylase (HDAC), pan-deacetylase (DAC), heat shock protein 90 (HSP90)
             inhibitors or valproic acid for the treatment of cancer.

          -  Concomitant malignancies or previous malignancies with less than a 2-year disease free
             interval at the time of enrollment. Patients with adequately resected basal or
             squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or
             Stage 1 prostate cancer or others deemed to be cured by surgery alone or surgery plus
             radiotherapy in the judgment of the Investigator may enroll irrespective of the time
             of diagnosis.

          -  Medical, psychiatric, cognitive, or other conditions that compromise the patient's
             ability to understand the patient information, to give informed consent, to comply
             with the study protocol, or to complete the study.

          -  Any severe concurrent disease or condition (including active systemic infection
             requiring systemic therapy, uncontrolled diabetes mellitus, symptomatic congestive
             heart failure, uncontrolled hypertension, unstable angina pectoris, or cardiac
             arrhythmia) which, in the judgment of the Investigator, would make the patient
             inappropriate for study participation.

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

          -  Significant gastrointestinal abnormalities, including an inability to take oral
             medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or
             vomiting considered to be clinically significant in the judgment of the Investigator,
             or prior surgical procedures affecting absorption.

          -  Known positive serology for the human immunodeficiency virus (HIV) (HIV 1/2
             antibodies) or acquired immunodeficiency syndrome (AIDS)-related illness, and/or known
             active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g.,
             hepatitis C virus ribonucleic acid [qualitative]).

          -  Pregnant or lactating females.

          -  12-lead electrocardiography (ECG) demonstrating a QT interval corrected for heart rate
             using Fridericia's formula (QTcF) of ≥ 450 msec for males and ≥ 470 msec for females
             (mean of the triplicate ECG measurements), with the exception for patients with an
             atrioventricular pacemaker or other conditions (e.g., right bundle branch block) that
             render the QT measurement invalid.

          -  History or current evidence of congenital long QT syndrome.

          -  Taking medications that lead to significant QT prolongation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
Time Frame:2 years
Safety Issue:
Description:Tolerability

Secondary Outcome Measures

Measure:Maximum Concentration (Cmax) of OKI-179 and OKI-006 in Plasma
Time Frame:2 years
Safety Issue:
Description:Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the maximum observed concentration for each compound.
Measure:Area Under the Curve (AUC) for OKI-179 and OKI-006 in Plasma
Time Frame:2 years
Safety Issue:
Description:Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the AUC for each compound.
Measure:Area Under the Curve (AUC) for OKI-179 and OKI-006 in Urine
Time Frame:2 years
Safety Issue:
Description:Urine concentrations of OKI-179 and OKI-006 will be measured to determine the AUC for each compound.
Measure:Time to Maximum Concentration (Tmax) for OKI-179 and OKI-006 in Plasma
Time Frame:2 years
Safety Issue:
Description:Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the Tmax for each compound.
Measure:Time to Maximum Concentration (Tmax) for OKI-179 and OKI-006 in Urine
Time Frame:2 years
Safety Issue:
Description:Urine concentrations of OKI-179 and OKI-006 will be measured to determine the Tmax for each compound.
Measure:Efficacy as measured by periodic CT/MRI scans using the revised Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time Frame:2 years
Safety Issue:
Description:Fraction of patients who have a Complete Response Fraction of patients who have a Partial Response Duration of response (DOR) Progression free survival Overall survival

Details

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

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