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A Study of OKI-179 in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03931681
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : May 21, 2019
Sponsor:
Collaborator:
University of Colorado, Denver
Information provided by (Responsible Party):
OnKure, Inc.

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

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: OKI-179 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of OKI-179 as a Single Agent in Patients With Advanced Solid Tumors
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Arm Intervention/treatment
Experimental: Experimental: Phase 1 - Dose Escalation
This 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.
Drug: OKI-179
OKI-179 single agent




Primary Outcome Measures :
  1. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) [ Time Frame: 2 years ]
    Tolerability

  2. Determine the safety of the drug according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5 [ Time Frame: 2 years ]
    • Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5
    • Incidence and severity of Serious Adverse Events
    • Incidence and severity of dose-limiting toxicities (DLTs)
    • Findings of changes in clinical laboratory abnormalities
    • Changes in triplicate 12-lead electrocardiogram (ECG) parameters
    • Changes in the Eastern Cooperative Oncology Group (ECOG) performance status (PS)
    • Changes in physical examination findings


Secondary Outcome Measures :
  1. Maximum Concentration (Cmax) of OKI-179 and OKI-006 in Plasma [ Time Frame: 2 years ]
    Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the maximum observed concentration for each compound.

  2. Area Under the Curve (AUC) for OKI-179 and OKI-006 in Plasma [ Time Frame: 2 years ]
    Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the AUC for each compound.

  3. Area Under the Curve (AUC) for OKI-179 and OKI-006 in Urine [ Time Frame: 2 years ]
    Urine concentrations of OKI-179 and OKI-006 will be measured to determine the AUC for each compound.

  4. Time to Maximum Concentration (Tmax) for OKI-179 and OKI-006 in Plasma [ Time Frame: 2 years ]
    Plasma concentrations of OKI-179 and OKI-006 will be measured to determine the Tmax for each compound.

  5. Time to Maximum Concentration (Tmax) for OKI-179 and OKI-006 in Urine [ Time Frame: 2 years ]
    Urine concentrations of OKI-179 and OKI-006 will be measured to determine the Tmax for each compound.

  6. 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 ]
    • 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



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

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): NCT03931681


Contacts
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Contact: John DeMattei, PhD 720-310-7759 jdemattei@onkuretherapeutics.com

Locations
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United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Jennifer Diamond, MD         
Sponsors and Collaborators
OnKure, Inc.
University of Colorado, Denver
Investigators
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Principal Investigator: Jennifer Diamond, MD University of Colorado, Denver

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Responsible Party: OnKure, Inc.
ClinicalTrials.gov Identifier: NCT03931681     History of Changes
Other Study ID Numbers: OKI-179-101
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Neoplasms