AOH1996 for the Treatment of Refractory Solid Tumors

• ClinicalTrials.gov Identifier: NCT05227326
• Recruitment Status: Active, not recruiting
• First Posted: February 7, 2022
• Last Update Posted: April 10, 2024
• Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): City of Hope Medical Center

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
Refractory Malignant Solid Neoplasm	Drug: PCNA Inhibitor AOH1996	Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

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

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

SECONDARY OBJECTIVES:

I. 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:

I. 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 (Clinical Trial)
• Actual Enrollment: 6 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
• Actual Study Start Date: August 12, 2022
• Estimated Primary Completion Date: September 28, 2024
• Estimated Study Completion Date: September 28, 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) [ Time Frame: 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 [ Time Frame: Up to 28 days (cycle 1) ]
   Toxicities will be graded according to NCI CTCAE version 4.0.

Secondary Outcome Measures :

1. Response rate [ Time Frame: 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 [ Time Frame: Assessed up to 2 years ]
   Time to disease progression/ relapse or death as a result of any cause.
3. Overall survival [ Time Frame: Assessed up to 2 years ]
   Time to death as a result of any cause.
4. Time to treatment failure [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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 1)
• 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

United States, Arizona

HonorHealth Research Institute

Scottsdale, Arizona, United States, 85258

United States, California

City of Hope Medical Center

Duarte, California, United States, 91010

Sponsors and Collaborators

City of Hope Medical Center

National Cancer Institute (NCI)

Investigators

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

More Information

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT05227326
• Other Study ID Numbers: 21310; NCI-2021-14102 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 21310 ( Other Identifier: City of Hope Medical Center ); P30CA033572 ( U.S. NIH Grant/Contract )
• First Posted: February 7, 2022
• Last Update Posted: April 10, 2024
• Last Verified: April 2024

• 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