Azenosertib for Uterine Cancer

Recruiting at 1 trial location

Overseen By Joyce Liu, MD, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Joyce Liu, MD

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, Active brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 7 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Azenosertib, an experimental drug, to determine its effects on tumor cells in individuals with persistent or recurrent uterine serous carcinoma, a type of uterine cancer. Participants take Azenosertib pills on specific days and undergo regular scans to monitor progress. Suitable candidates for this trial have this specific type of uterine cancer and have received at least one prior treatment with platinum-based chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take medications that strongly affect CYP3A4, a liver enzyme. You also need to stop any herbal supplements at least 7 days before starting the trial.

Is there any evidence suggesting that Azenosertib is likely to be safe for humans?

Research has shown that Azenosertib, a new treatment under testing, is generally safe for people with uterine cancer. In one study, over 500 patients received Azenosertib, and most did not experience severe side effects. The treatment also showed promise in controlling the disease.

However, some serious risks exist. In one trial, two deaths occurred due to bloodstream infections, known as sepsis. These incidents prompted additional safety checks in some studies.

Overall, while Azenosertib appears effective for many, considering these risks is crucial. Anyone considering joining a trial should discuss the potential benefits and risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Azenosertib is unique because it targets uterine cancer cells differently than traditional treatments like surgery, chemotherapy, and radiation. Unlike these standard options, Azenosertib is taken orally and works by specifically inhibiting enzymes that promote cancer cell growth, potentially reducing side effects. Researchers are excited about this treatment because it could offer a more targeted approach, possibly leading to better outcomes and improved quality of life for patients with uterine cancer.

What evidence suggests that Azenosertib might be an effective treatment for uterine cancer?

Research has shown that Azenosertib, a type of medication, may help treat recurring or ongoing uterine serous carcinoma, a form of cancer. Studies found that it controlled the disease in 90.9% of patients and helped shrink or control tumors in about 27.3% of them. In another study, Azenosertib shrank tumors in 37% of patients, with these patients living an average of 6.5 months without the cancer worsening. These results suggest that Azenosertib could be an effective option for managing this cancer, offering hope to patients with few treatment choices. Participants in this trial will receive Azenosertib as the investigational treatment. ^{1 2 6 7 8}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with persistent or recurrent uterine serous carcinoma who've had one prior platinum-based chemotherapy. They must have measurable disease, be able to consent, and agree to use contraception. Excluded are those allergic to similar compounds as Azenosertib, pregnant/breastfeeding women, and those on certain medications.

Inclusion Criteria

I can take care of myself and perform daily activities.

I agree to use birth control during the study.

My organs and bone marrow are functioning well.

Exclusion Criteria

History of allergic reactions to compounds similar to azenosertib.

Participants receiving any other investigational agents for this condition.

Participants unable to swallow oral medication or dependent on certain medical support are excluded.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Azenosertib with assessments and imaging scans

Up to 7 months

Baseline visit, CT or MRI scans every 2 cycles, End of Treatment visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 months

Long-term Follow-up

Participants are monitored for progression-free survival and overall response

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Azenosertib

Trial Overview The study tests how Azenosertib (a Wee1 inhibitor) affects tumor cells in uterine serous carcinoma patients. Participants will take the drug orally and provide tissue samples before and during treatment for research purposes.

How Is the Trial Designed?

Group I: Azenosertib Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Joyce Liu, MD

Lead Sponsor

Trials

1

Recruited

30+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Zentalis

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a pilot study of 10 postmenopausal women with early-stage endometrial cancer, treatment with the aromatase inhibitor letrozole for 14 days showed satisfactory tolerability and led to a significant reduction in blood estradiol levels by 37.8%.

The treatment also resulted in a 31.1% decrease in endometrial signal on ultrasound and a reduction in aromatase activity and progesterone receptor levels, suggesting potential biological responses that warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. Bershteĭn, LM., Maksimov, SIa., Gershfel'd, ED., et al.[2018]

The standard first-line chemotherapy for metastatic or recurrent endometrial cancer, combining carboplatin and paclitaxel, shows objective response rates of 43-62% and median overall survival ranging from 13.2 to 37.0 months, indicating its effectiveness in this patient population.

Immune checkpoint inhibitors like pembrolizumab and dostarlimab have demonstrated promising results, achieving objective response rates of 27-47% in patients with microsatellite instability-high (MSI-H) endometrial cancer, highlighting a potential treatment avenue for highly pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Treatment of Advanced, Persistent or Metastatic Endometrial Cancer: State of the Art and Perspectives of Clinical Research for the Special Issue "Diagnosis and Management of Endometrial Cancer". Gadducci, A., Cosio, S.[2021]

A new human cell line called ZJB-ENC1 has been established from poorly differentiated endometrioid adenocarcinoma, providing a valuable resource for studying endometrial cancer.

The ZJB-ENC1 cell line exhibits unique genomic characteristics and confirmed tumorigenicity in a mouse model, making it a promising tool for research into the biology and treatment of endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and characterization of novel human primary endometrial cancer cell line (ZJB-ENC1) and its genomic characteristic. Liu, X., Ren, Z., Xu, Y., et al.[2020]

A survey of oncologists in Italy revealed that while there is a good understanding of new treatments for endometrial cancer (EC), such as dostarlimab for MSI high patients, these innovations are not fully integrated into clinical practice, with only 13.3% performing all necessary molecular tests.

After the approval of dostarlimab, 75.6% of clinicians preferred it for second-line treatment in MSI high advanced EC patients, indicating a significant shift in treatment choice, while 77.8% plan to use lenvatinib plus pembrolizumab for MSS patients once approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey. Giannone, G., Castaldo, D., Tuninetti, V., et al.[2022]

In a study of 355 endometrial cancer patients, key predictors of recurrence included FIGO stage, lymphovascular space invasion, and the presence of cytotoxic and memory T-cells, with a combination of these factors providing the best predictive accuracy.

The combination of FIGO stage, lymphovascular space invasion, and cytotoxic T-cell counts achieved a high concordance index (C-index of 0.82), indicating a strong ability to predict recurrence in high-risk endometrial cancer patients, and these findings were validated in an independent cohort of 72 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters. Versluis, MA., de Jong, RA., Plat, A., et al.[2022]

Aromatase inhibitors, like aminoglutethimide, may be an effective treatment for endometrial stromal sarcoma (ESS), as demonstrated by two case studies where both patients achieved a complete response after treatment.

Routine analysis of estrogen and progesterone receptors in metastatic tissues could help predict which patients with ESS will respond well to hormonal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma. Spano, JP., Soria, JC., Kambouchner, M., et al.[2018]

Patients with metastatic or recurrent endometrial cancer have a poor prognosis, but local recurrences may be treated effectively with radiation, especially when combined with chemotherapy.

Chemotherapy regimens using anthracyclines, platinum compounds, and paclitaxel show response rates over 20%, but while combination therapies yield higher response rates, they are also more toxic and have limited impact on overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced or recurrent endometrial carcinoma. Fleming, GF.[2019]

The study aims to evaluate the efficacy of the Wee1 inhibitor adavosertib in approximately 120 women with recurrent or persistent uterine serous carcinoma, a type of endometrial cancer known for its aggressive nature and poor prognosis.

Participants will receive adavosertib as a monotherapy, with the primary endpoint being the objective response rate assessed by independent review, indicating the potential for adavosertib to provide a new treatment option for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma. Liu, J., Oza, AM., Colombo, N., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04814108

A Study of ZN-c3 in Women With Recurrent or Persistent ... 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 ...

2. onclive.com onclive.com/view/zn-c3-shows-preliminary-efficacy-safety-in-recurrent-advanced-uterine-serous-carcinoma

ZN-c3 Shows Preliminary Efficacy, Safety in Recurrent ... The investigational Wee1 inhibitor ZN-c3 was found to be safe and to produce a disease control rate of 90.9% and an objective response rate of 27.3%.

3. onclive.com onclive.com/view/fda-places-partial-clinical-holds-on-3-trials-evaluating-azenosertib-in-advanced-solid-tumors

FDA Places Partial Clinical Holds on 3 Trials Evaluating ... The ZN-c3-001 trial showed a 37% ORR and 6.5 months median PFS in patients with platinum-resistant ovarian cancer and uterine serous carcinoma.

4. ir.zentalis.com ir.zentalis.com/news-releases/news-release-details/zentalis-pharmaceuticals-announces-promising-initial-data

Release Details ZN-c3 demonstrated single agent activity, generating Exceptional Responses in a range of heavily pre-treated solid tumors. ZN-c3 was safe and well-tolerated.

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04158336

A Study of ZN-c3 in Participants With Solid Tumors The confirmed objective response rate (ORR) was 36.8% (7/19) in the combined ovarian cancer and uterine serous carcinoma (USC) subgroups who received an ...

6. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT029/701937/Abstract-CT029-Safety-and-clinical-activity-of

Safety and clinical activity of single-agent ZN-c3, an oral ... Conclusions: ZN-c3 appears to be safe and well-tolerated as a single agent at oral doses ≥300 mg QD and demonstrated clinical activity in ...

7. ir.zentalis.com ir.zentalis.com/news-releases/news-release-details/zentalis-pharmaceuticals-provides-update-azenosertib-clinical

Zentalis Pharmaceuticals Provides Update on Azenosertib ... “Over 500 patients have been treated with azenosertib monotherapy to date, and we believe that our data indicate a favorable therapeutic index ...

8. cancernetwork.com cancernetwork.com/view/fda-places-partial-holds-on-3-trials-for-solid-tumor-treatment-azenosertib

FDA Places Partial Holds on 3 Trials for Solid Tumor ... Two deaths due to presumed sepsis in patients treated in the DENALI trial led to the clinical holds on the advanced solid tumor treatment.