Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: K-Group Beta
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma (USC).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you must not have had chemotherapy, targeted tumor therapy, or investigational drug therapy within a certain time frame before starting the trial.
Eligibility Criteria
This trial is for adult women with recurrent or persistent uterine serous carcinoma who are in good physical condition (ECOG PS of 0 or 1), have measurable disease, and proper organ function. Participants must be at least 18 years old and agree to use contraception. Women can't join if they've had certain prior treatments, other serious medical conditions, unresolved toxicities from past therapies, are pregnant/breastfeeding, have uncontrolled second cancers, or specific heart issues.Inclusion Criteria
I am a woman aged 18 or older.
I am fully active or restricted in physically strenuous activity but can do light work.
I have at least one tumor that can be measured.
My uterine cancer has come back or hasn't gone away.
I am fully active or can carry out light work.
I am a woman aged 18 or older.
My uterine cancer has come back or never went away.
Exclusion Criteria
I have never been treated with ZN-c3 or any WEE1 inhibitor.
I have been treated with a cell cycle checkpoint inhibitor before.
I do not have another cancer that is spreading or needs treatment.
I have a personal or family history of long QT syndrome.
I don't have major side effects from previous treatments, except for mild nerve issues, hair loss, or skin color changes.
Participant Groups
The study tests the effectiveness and safety of a drug called ZN-c3 (azenosertib) specifically in women with uterine serous carcinoma that has come back or hasn't gone away after treatment. It's a Phase 2 clinical trial focusing on how well this drug works against this type of cancer.
1Treatment groups
Experimental Treatment
Group I: ZN-c3 Single AgentExperimental Treatment1 Intervention
ZN-c3 (azenosertib) taken orally with food
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Augusta UniversityAugusta, GA
Site 0114Farmington Hills, MI
Site 3403Toronto, Canada
Site 3401Quebec City, Canada
More Trial Locations
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Who is running the clinical trial?
K-Group BetaLead Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, IncLead Sponsor
References
ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer. [2019]Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) upregulates genes encoding proteins involved in cell differentiation, proliferation and apoptosis. ZKSCAN3 has been reported to be overexpressed in several human cancers such as colorectal cancer and prostate cancer and is proposed as a candidate oncoprotein. However, the molecular mechanism by which ZKSCAN3 participates in carcinogenesis is largely unknown. Here, we evaluated ZKSCAN3 expression in uterine cervical cancers (CC) by immunohistochemistry using formalin-fixed, paraffin-embedded tissues from 126 biopsy samples from 126 patients. The clinicopathological findings were analyzed and compared with ZKSCAN3 expression levels. ZKSCAN3 was strongly overexpressed in CCs compared to adjacent non-neoplastic cervical mucosa tissues. Moreover, a gene copy number assay showed amplified ZKSCAN3 in CC samples. ZKSCAN3 overexpression was also significantly associated with poor overall survival of the patients. Overall, our findings indicate that ZKSCAN3 overexpression is a frequent event in uterine CC and is correlated with a poor clinical outcome. ZKSCAN3 could be developed as a molecular marker for prognostic prediction and early detection.
ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion. [2021]ZKSCAN3, a zinc-finger transcription factor, which has been shown to be upregulated in several human cancer. However, the expression level, function and mechanism of ZKSCAN3 in breast cancer remains unknown. In the current study, immunohistochemistry, western blot and quantitative real time polymerase chain reaction (qRT-PCR) results showed that ZKSCAN3 was overexpressed in breast cancer tissue compared with normal breast tissue. Through analyzing the clinicopathological characteristics, we demonstrated that positive ZKSCAN3 expression predicted poor prognosis of patients with breast cancer. The expression level of ZKSCAN3 protein/mRNA in breast cancer cells (MCF-7 and MDA-MB-231) was higher than its expression in normal breast cells (HBL-100). Knocking down ZKSCAN3 via its short hairpin RNA (shRNA) in MCF-7 and MDA-MB-231 inhibited cell viability, migration and invasion. Western blot analysis showed that ZKSCAN3 silencing lead to significant decreases in the expression of Cyclin D1, B-cell lymphoma-2 (Bcl-2), and matrix metalloproteinase (MMP)-2/MMP-9, as well as increases in the expression of Bcl2 Associated X Protein (Bax) in breast cancer cells. Additionally, ZKSCAN3-shRNA expression markedly suppressed tumor growth in breast cancer xenograft mice. Finally, we demonstrated that silencing of ZKSCAN3 was able to inhibit Akt/mTOR signaling pathway by blocking p-Akt and p-mTOR protein expression in breast cancer cells. These results demonstrate that ZKSCAN3 plays a significant role in the progression of breast cancer. Therefore, ZKSCAN3 is a potential therapeutic target for breast cancer.
The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer. [2023]Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors.
The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models. [2023]Zinc finger protein 275 (ZNF275) is a C2H2-type transcription factor that is localized on chromosome Xq28. Whether ZNF275 participates in modulating the biological behaviors of cervical cancer has not been determined to our knowledge. The present study employed CCK-8, BrdU, flow cytometry, and a transwell assay to investigate the cell viability, proliferation, apoptosis, migration, and invasion of cervical cancer cells. The application of Western blotting and immunohistochemistry (IHC) aims to assess ZNF275 protein expression and identify the signaling pathway relevant to ZNF275-mediated effects on cervical cancer. The therapeutic impact of the combined therapy of the AKT inhibitor triciribine and cisplatin was evaluated on cervical cancer patient-derived xenograft (PDX) models expressing high ZNF275. The current research illustrated that cervical cancer tissue exhibited a higher expression of ZNF275 in contrast to the surrounding normal cervical tissue. The downregulation of ZNF275 suppressed cell viability, migration, and invasion, and facilitated the apoptosis of SiHa and HeLa cells via weakening AKT/Bcl-2 signaling pathway. Moreover, triciribine synergized with cisplatin to reduce cell proliferation, migration, and invasion, and enhanced the apoptosis of SiHa cells expressing high ZNF275. In addition, the combination treatment of triciribine and cisplatin was more effective in inducing tumor regression than single agents in cervical cancer PDX models expressing high ZNF275. Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results.
ZC3H13 Enhances the Malignancy of Cervical Cancer by Regulating m6A Modification of CKAP2. [2023]Sustained expression of zinc finger CCCH-type containing 13 (ZC3H13) in tumors is essential for cancer cell malignancy; however, our understanding of its clinical effects and mechanisms in cervical cancer (CC) is limited. In this study, we aimed to reveal the effect on CC progression of ZC3H13-mediated N6-methyladenosine (m6A) modification to stabilize cytoskeleton-associated protein 2 (CKAP2) expression. CC tissues and paired adjacent normal tissues were collected from 50 patients. qRT-PCR was used to clarify ZC3H13 and CKAP2 expression levels in the CC tissues. The functional roles of ZC3H13 and CKAP2 in CC were analyzed by detecting the changes in CC cell proliferation, migration, invasion, and tumor growth in vivo. The regulatory relationship between ZC3H13 and CKAP2 was investigated by confirming m6A modification levels and their expression correlation. ZC3H13 and CKAP2 were highly expressed in CC and linked with poor prognosis. We observed that ZC3H13 inhibition decreased CC cell proliferation, invasion, and migration, while its facilitation promoted CC cell malignancy. ZC3H13 mediated m6A modification of CKAP2 to enhance CKAP2 expression in CC cells. Furthermore, CKAP2 overexpression partially restored the malignant phenotypic promotion induced by ZC3H13 overexpression in CC cells. In summary, this study revealed that ZC3H13-mediating m6A modification of CKAP2 promotes CC development. This finding should be conducive to an understanding of the role of ZC3H13-m6A-CKAP2 in CC and should provide an effective therapeutic target for this cancer.