Refractory Malignant Solid NeoplasmPhase 1NCT05227326
AOH1996 for the Treatment of Refractory Solid Tumors
A Phase 1 study testing PCNA Inhibitor AOH1996 in people with Refractory Malignant Solid Neoplasm and Osteosarcoma, run by City of Hope Medical Center at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Malignant Solid Neoplasm, Osteosarcoma, Leiomyosarcomas
- What is being tested?
- PCNA Inhibitor AOH1996
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Sep 2022to 13 Sep 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed Consent and Willingness to Participate
- 1. Documented informed consent by the participant
- 2. Willingness to permit study team to obtain and use archival tissue, if already existing
- Age Criteria, Performance Status and Life Expectancy
- 3. Age: ≥ 18 years
- 4. ECOG performance status ≤ 2
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- 5. Life expectancy of > 3 months
- Nature of Illness and Treatment History 6. Patients with solid tumors failing standard therapies or patients refusing standard treatments (exception: Part B NSCLC combination (EGFR TKI + AOH1996) cohort: patients with stable disease or better on EGFR TKI for at least 2 months)
- Contraception
- 7. 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. See Appendix B for guidelines.
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
- Laboratory Criteria (to be performed within 14 days prior to Day 1)
- 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
Who cannot join
- Concomitant Medications/Therapies 1. Dietary/herbal supplements
- 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
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- Other Illnesses and Conditions
- 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).
- Noncompliance
- 12. 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).
- Eligibility should be confirmed per institutional policies.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Patient Services, 1-800-826-4673, ClinicaltrialAOH1996@coh.org
Vincent Chung, MD
- Recruiting
City of Hope at Long Beach Elm
Long Beach, California, 90813
Vincent Chung, MD, 626-218-4673, vchung@coh.org
- Not yet recruiting
Honor Health Research and Innovation Institute
Scottsdale, Arizona, 85258
Patient Services, 1-800-826-4673, ClinicaltrialAOH1996@coh.org
Erkut Borazanci, MD
About this study
Official title: First in Human Phase 1 Study of AOH1996 in Patients With 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of AOH1996.
II. To establish the recommended phase 2 dose of AOH1996.
III. To establish the recommended phase 2 dose of AOH1996 when given in conjunction with a TKI for NSCLC.
SECONDARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Refractory Malignant Solid Neoplasm, Osteosarcoma, Leiomyosarcomas, Synovial Sarcomas, Ovarian Cancer, Non-Small Cell Lung Cancer
- Being tested
- PCNA Inhibitor AOH1996
- Medical subject headings
- Osteosarcoma, Leiomyosarcoma, Sarcoma, Synovial, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCNA Inhibitor AOH1996Drug
Also called AOH 1996, AOH-1996, AOH1996, Proliferating Cell Nuclear Antigen Inhibitor AOH1996
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (PCNA inhibitor AOH1996) | Experimental | 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. Receives: Drug: PCNA Inhibitor AOH1996 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 days after last study drug is given
Dose limiting toxicities
Toxicities will be graded according to NCI CTCAE version 4.0.
Measured: Up to 28 days (cycle 1)
Secondary outcomes (4)
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.
Measured: Up to 2 years
Progression-free survival
Time to disease progression/ relapse or death as a result of any cause.
Measured: Assessed up to 2 years
Overall survival
Time to death as a result of any cause.
Measured: Assessed up to 2 years
Time to treatment failure
Time to treatment termination for any reason (progression, toxicity, death, patient preference).
Measured: Assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2022
- Study start8 Sep 2022
- Primary completion13 Sep 2029 (estimated)
- Study completion13 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vincent Chung, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05227326
- Sponsor's protocol ID
- 21310
- Other IDs
- NCI-2021-14102, 21310, P30CA033572
- Status last verified
- Oct 2026
- First submitted
- 11 Jan 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No