Azenosertib in Uterine Serous Carcinoma: Biomarker Study

NCT06369155 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-061
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is being done to investigate how Azenosertib affects tumor cells of persistent or recurrent uterine serous carcinoma. The name of the study drug involved in this study is:

• Azenosertib (a type of Wee1 inhibitor)

Conditions

Uterine Serous Carcinoma; Uterine Carcinoma; Uterine Cancer

Keywords

Uterine Serous Carcinoma; Uterine Carcinoma; Uterine Cancer; Persistent Uterine Serous Carcinoma

Outcome Measures

Primary Outcomes (2)

• Percentage Change in Replication Fork Speed in Overall Response

  Replication fork speed assessed by DNA fiber assays in PDO models. Responder defined as participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria. Wilcoxon rank sum tests will be used to compare the percentage change in replication fork speed with exposure to WEE1 inhibition in co-clinical models between overall response responder and non-responder.

  Up to 7 months

• Percentage Change in Replication Fork Speed in 6 Month Progression Free Survival (PFS6)

  Replication fork speed assessed by DNA fiber assays in PDO models. PFS6 is a binary endpoint where patients that are alive and progression free (per RECIST 1.1) at 6 months are considered responders. All other patients (those that died or progressed prior to 6 months or those with less than 6 months of follow-up for progression) are considered non-responders. Wilcoxon rank sum tests will be used to compare the percentage change in replication fork speed with exposure to WEE1 inhibition in co-clinical models between overall response responder and non-responder.

  At 6 months

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 7 months

• 6-month Progression-Free Survival (PFS6)

  At 6 months

• Clinical Benefit Rate (CBR)

  Up to 7 months

• Median Duration of Overall Response (DOR)

  Up to 7 months

• Median Progression-Free Survival (PFS)

  2 years

Study Arms (1)

Azenosertib

EXPERIMENTAL

25 participants will be enrolled and will complete study procedures as follows: * Baseline visit with assessments and CT or MRI scan. * CT or MRIs scans every 2 cycles. * Cycle 1 through End of Treatment: --Days 1 through 5, 8 through 12, and 15 through 19: Predetermined dose of Azenosertib 1x daily. * End of Treatment visit.

Drug: Azenosertib

Interventions

Azenosertib DRUG

Wee1 inhibitor, 25mg and 100mg tablets, taken orally per protocol.

Also known as: Zn-c3, C29H34N8O2

Azenosertib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed recurrent or persistent uterine serous carcinoma. For the purposes of this study, uterine carcinomas (with the exception of carcinosarcomas) that have any component that is considered serous will be considered a uterine serous carcinoma.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured per RECIST 1.1 criteria. See Section 12 for the evaluation of measurable disease.
• Participants must have had one prior platinum-based chemotherapy regimen for management of advanced or metastatic uterine serous carcinoma. Participants with early stage disease who received adjuvant platinum-based chemotherapy are also eligible if they recur within 12 months of their adjuvant therapy. Chemotherapy administered only in conjunction with primary RT as a radiosensitizer should not count as a systemic regimen. There is no restriction on the number of prior lines of therapy a participant may have previously received. Additionally, participants must have a known tumor MSI or MMR status and those participants with MSI-high or MMR-deficient tumors must have already received prior therapy with a PD1 or PD-L1 immune checkpoint inhibitor or be deemed not to be a candidate for immune checkpoint therapy.
• Age 18 years or older. Because no dosing or adverse event data are currently available on the use of azenosertib in participants \<18 years of age, children are excluded from this study.
• ECOG performance status 0, 1, or 2 (see Appendix A)
• Participants must meet the following organ and marrow function as defined below:
• absolute neutrophil count ≥1500/mcL
• hemoglobin ≥9 g/dL (must be at least 2 weeks since any blood transfusion)
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN) or
• ≤1.5x ULN in patients with liver metastases or well-documented Gilbert's Syndrome
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN or ≤5 × institutional ULN in patients with liver metastases
• creatinine ≤ 1.5x institutional ULN or estimated CrCl≥ 60 mL/min
• Willingness to release archival tissue for research purposes.
• Biopsiable disease in a lesion that is not being utilized as the target lesion for RECIST assessment and willing to undergo pre- and on-treatment biopsies.

You may not qualify if:

• Participants who have had chemotherapy, radiotherapy, or investigational therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of azenosertib. Participants may not have had hormonal therapy within 2 weeks of the first dose of azenosertib.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy administered more than 3 weeks before first dose of azenosertib (e.g.,., have residual toxicities \> Grade 1) with the exception of alopecia.
• Participants who are receiving any other investigational agents for this condition.
• Participants may not have had prior receipt of a cell cycle checkpoint inhibitor (e.g., Chek1, Wee1, or ATR inhibition)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azenosertib.
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine.
• Pregnant women are excluded from this study because azenosertib is an DNA damage repair pathway agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azenosertib, breastfeeding should be discontinued if the mother is treated with azenosertib.
• Women of childbearing potential (WoCBP) may be included only if acceptable contraception (see Appendix C) is in place for two weeks before study entry, for the duration of the treatment with the study drug and for 5x half-lives of ZN-c3 + 6 months after the last dose of ZN-c3. Sexually active female subjects of childbearing potential must agree to use protocol-recommended method of contraception from the start of the screening period until 6 months after the last dose of study drug ZN-c3.
• Participants must not have undergone major surgical procedures within 28 days of beginning study treatment or minor surgical procedures within 7 days of beginning study treatment. Port-a-cath placement will be allowed within a 7 day window of starting study treatment.
• Participants must be able to swallow oral medication and may not have refractory nausea and vomiting, have a percutaneous endoscopic gastrostomy (PEG) tube, be receiving total parenteral nutrition (TPN), or be dependent on IV fluid support.
• Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, cannabis, St. John's wort, kava, ephedra \[ma huang\], ginkgo biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, and ginseng). Participants should stop herbal medications at least 7 days prior to first dose of azenosertib.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.

Sponsors & Collaborators

• Joyce Liu, MD: lead
• National Cancer Institute (NCI): collaborator
• Zentalis: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Uterine Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Joyce Liu, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joyce Liu, MD, MPH

CONTACT

617-632-5269; Joyce_Liu@DFCI.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 12, 2024
• First Posted: April 16, 2024
• Study Start: March 5, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)