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AOH1996 for the Treatment of Refractory Solid Tumors

Sponsor
City of Hope Medical Center (Other)
Overall Status
Withdrawn
CT.gov ID
NCT05227326
Collaborator
National Cancer Institute (NCI) (NIH)
0
Enrollment
1
Arm
20
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of AOH1996 in treating patients with solid tumors that do not respond to treatment (refractory). AOH1996 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease Intervention/Treatment Phase
  • Drug: PCNA Inhibitor AOH1996
 Phase 1

Detailed Description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of PCNA inhibitor AOH1996 (AOH1996).

  2. To establish the recommended phase 2 dose (RP2D) of AOH1996.

SECONDARY OBJECTIVES:
  1. To determine the pharmacokinetics of AOH1996. II. To evaluate for preliminary efficacy of AOH1996. III. To evaluate response rate and disease control rate in solid tumors.
EXPLORATORY OBJECTIVE:
  1. To determine pharmacodynamics parameters (alteration of gammaH2AX, downregulation of Myc) of AOH1996.

OUTLINE: This is a dose-escalation study.

Patients receive AOH1996 orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
First in Human Phase 1 Study of AOH1996 in Patients With Refractory Solid Tumors
Anticipated Study Start Date :
Jul 30, 2022
Anticipated Primary Completion Date :
Mar 30, 2024
Anticipated Study Completion Date :
Mar 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (PCNA inhibitor AOH1996)

Patients receive PCNA inhibitor AOH1996 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: PCNA Inhibitor AOH1996
Given PO
Other Names:
  • AOH 1996
  • AOH-1996
  • AOH1996
  • Proliferating Cell Nuclear Antigen Inhibitor AOH1996

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse events (AEs) [Up to 30 days after last study drug is given]

      Toxicity and adverse events will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All toxicities/AEs will be recorded from the initiation of protocol therapy through the follow-up period.

    2. Dose limiting toxicities [Up to 28 days (cycle 1)]

      Toxicities will be graded according to NCI CTCAE version 4.0.

    Secondary Outcome Measures

    1. Response rate [Up to 2 years]

      Will be assessed using Response Evaluation Criteria in Solid Tumors version 1. Response rate will be estimated in the overall population and 95% exact confidence intervals will be estimated.

    2. Progression-free survival [Assessed up to 2 years]

      Time to disease progression/ relapse or death as a result of any cause.

    3. Overall survival [Assessed up to 2 years]

      Time to death as a result of any cause.

    4. Time to treatment failure [Assessed up to 2 years]

      Time to treatment termination for any reason (progression, toxicity, death, patient preference).

    Other Outcome Measures

    1. Levels of plasma gammaH2AX [Up to 2 years]

      Will use descriptive statistics and graphical displays to summarize levels of plasma gammaH2AX, evaluate changes between pre- and post-treatment measurements. A paired t-test will be used to determine if there is a statistically significant change.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Documented informed consent by the participant

    • Willingness to permit study team to obtain and use archival tissue, if already existing

    • Age: >= 18 years

    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2

    • Life expectancy of > 3 months

    • Patients with solid tumors failing standard therapies or patients refusing standard treatments

    • Agreement by females and males of childbearing potential to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

    • Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 14 days prior to day

    • Total serum bilirubin =< 1.5 x upper limit of normal (ULN) (performed within 14 days prior to day 1)

    • Aspartate aminotransferase (AST) =< 1.5 x ULN or =< 3 x ULN with liver metastases (performed within 14 days prior to day 1)

    • Alanine aminotransferase (ALT) =< 1.5 x ULN or =< 3 x ULN with liver metastases (performed within 14 days prior to day 1)

    • Creatinine clearance of >= 60 mL/min per 24 hour urine or the Cockcroft-Gault (performed within 14 days prior to day 1)

    • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

    • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

    Exclusion Criteria:

    • Concomitant medications/therapies

    • Dietary/herbal supplements

    • Other investigational products

    • Warfarin

    • Current or planned use of agents contraindicated for use with strong CYP3A4 inducers

    • Strong inhibitors or inducers of CYP2C9

    • Strong inhibitors or inducers of CYP3A

    • Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting)

    • Women who are or are planning to become pregnant or breastfeed

    • Known allergy to any of the components within the study agents and/or their excipients

    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

    • Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection)

    • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • City of Hope Medical Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Vincent Chung, City of Hope Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT05227326
    Other Study ID Numbers:
    • 21310
    • NCI-2021-14102
    • 21310
    • P30CA033572
    First Posted:
    Feb 7, 2022
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 1, 2022
    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

    Study Results

    No Results Posted as of Jun 9, 2022