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

Trial Summary

What is the purpose of this trial?

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)

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.

What data supports the effectiveness of the drug Azenosertib for uterine cancer?

The effectiveness of Azenosertib, a Wee1 inhibitor, may be supported by research on a similar drug, adavosertib, which showed durable clinical activity in treating uterine serous carcinoma, a type of endometrial cancer. ^{1 2 3 4 5}

How is the drug Azenosertib different from other treatments for uterine cancer?

Azenosertib is unique because it is a Wee1 inhibitor, which targets a specific protein involved in cell cycle regulation, potentially offering a novel approach for treating aggressive forms of uterine cancer like uterine serous carcinoma, where traditional options are limited. ^{4 5 6 7 8}

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters. [2022]

4. England 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. [2022]

5. Switzerland 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". [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Establishment and characterization of novel human primary endometrial cancer cell line (ZJB-ENC1) and its genomic characteristic. [2020]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma. [2018]