AOH1996 For The Treatment Of Refractory Solid Tumors

Study Overview

AOH1996 for the Treatment of Refractory Solid Tumors

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.

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.

Refractory Malignant Solid Neoplasm
Osteosarcoma
Leiomyosarcomas
Synovial Sarcomas
Ovarian Cancer
Non-Small Cell Lung Cancer
Pancreatic Cancer

DRUG: PCNA Inhibitor AOH1996

21310
NCI-2021-14102 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
21310 (OTHER Identifier) (OTHER: City of Hope Medical Center)
P30CA033572 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-01-11	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-10-09
First Submitted that Met QC Criteria 2022-02-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-10-15
First Posted (ACTUAL) 2022-02-07	Results First Posted N/A	Last Verified 2024-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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

Participant Group/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

Primary Outcome Measures	Measure Description	Time Frame
Incidence of adverse events (AEs)	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.	Up to 30 days after last study drug is given
Dose limiting toxicities	Toxicities will be graded according to NCI CTCAE version 4.0.	Up to 28 days (cycle 1)

Secondary Outcome Measures	Measure Description	Time Frame
Response rate	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.	Up to 2 years
Progression-free survival	Time to disease progression/ relapse or death as a result of any cause.	Assessed up to 2 years
Overall survival	Time to death as a result of any cause.	Assessed up to 2 years
Time to treatment failure	Time to treatment termination for any reason (progression, toxicity, death, patient preference).	Assessed up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Vincent Chung, MD

Phone Number: 626-359-8111

Email: vchung@coh.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

1. Documented informed consent by the participant
2. Willingness to permit study team to obtain and use archival tissue, if already existing

3. Age: ≥ 18 years
4. ECOG performance status ≤ 2
5. Life expectancy of > 3 months

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. See Appendix B for guidelines.

8. ANC ≥ 1,500/mm3
9. Platelets ≥ 100,000/mm3 :
10. Total serum bilirubin ≤ 1.5 x ULN
11. AST =< 1.5 x ULN or =< 3 x ULN with liver metastases
12. ALT =< 1.5 x ULN or =< 3 x ULN with liver metastases
13. Creatinine clearance of ≥ 60 mL/min per 24 hour urine or the Cockcroft-Gault
14. 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

2. Other investigational products or chemotherapy. Exception: EGFR TKI in the NSCLC expansion cohort is allowed.
3. Warfarin
4. Current or planned use of agents contraindicated for use with strong CYP3A4 inducers
5. Strong inhibitors or inducers of CYP2C9
6. Strong inhibitors or inducers of CYP3A

7. Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).
8. Women who are or are planning to become pregnant or breastfeed
9. Known allergy to any of the components within the study agents and/or their excipients.
10. 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.
11. 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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Vincent Chung, MD, City of Hope Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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