Azenosertib for Uterine Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Joyce Liu, MD
No Placebo Group
Prior Safety Data
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.
12345How 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.
45678Eligibility 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.Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: AzenosertibExperimental Treatment1 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
Dana-Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
Joyce Liu, MDLead Sponsor
National Cancer Institute (NCI)Collaborator
ZentalisCollaborator
References
Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey. [2022]Endometrial cancer (EC) therapeutic and diagnostic approaches have been changed by the development of a new prognostic molecular classification, the introduction of dostarlimab in microsatellite instability (MSI) high pre-treated advanced EC patients with further expected innovation deriving from lenvatinib plus pembrolizumab regardless MSI status. How this is and will be translated and embedded in the clinical setting in Italy is not known; this is why we developed Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies (MITO) survey on the current practice and expected future changes in EC.
Systemic therapy for advanced or recurrent endometrial carcinoma. [2019]The prognosis for metastatic or recurrent endometrial cancer remains poor. Patients with local recurrences can sometimes be salvaged with radiation, and these salvage rates might improve with the addition of concomitant chemotherapy. Hormone therapy benefits a small group of patients, and routine immunohistochemical determination of tumor receptor status may help select patients most likely to benefit from such therapy. Anthracyclines, platinum compounds, and paclitaxel consistently produce response rates of over 20%. Combination chemotherapy produces higher response rates, but it is toxic and appears to have minimal effect on survival. New drugs and combinations continue to be tested. A subset of endometrial cancers overexpress the HER2/neu oncogene, and a trial of anti-HER2/neu monoclonal antibody for this group is planned through the Gynecologic Oncology Group.
Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters. [2022]Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.
ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma. [2022]Uterine serous carcinoma is a distinct histologic subtype of endometrial cancer with an aggressive phenotype, poor prognosis, and limited therapeutic options. A previous proof-of-concept phase II trial of the Wee1 inhibitor adavosertib in uterine serous carcinoma demonstrated evidence of durable clinical activity.
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]Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43-62%, a median progression-free survival (PFS) of 5.3-15 months and a median overall survival (OS) of 13.2-37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27-47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.
Establishment and characterization of novel human primary endometrial cancer cell line (ZJB-ENC1) and its genomic characteristic. [2020]The establishment of human malignant tumor cell lines can provide abundant experimental materials for understanding the biological characteristics of tumors, studying the carcinogenesis, molecular genetics and the mechanism of metastasis and evolution. In this study, a novel cell line designated ZJB-ENC1 has been established from poorly differentiated endometrioid adenocarcinoma. Cytological results showed monolayer-cultured cells were polygonal in shape and a piling-up tendency without contact inhabitation. Immunohistochemistry analysis showed that the cells were negative for ER, PR, c-erbB2, E-CAD, CD117, and OCT3/4, but strongly positive for PTEN and P16. Meanwhile, the tumorigenicity of ZJB-ENC1 was confirmed by subcutaneous transplantation of the cells into a xenograft mouse model. In addition, the results of the whole exome sequencing revealed a unique genomic characteristic of ZJB-ENC1 cells, all common and novel SNPs and InDels were identified. In conclusion, this new stable cell line may promote basic and clinical research on endometrial cancer (EC).
[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. [2018]Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.
Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma. [2018]Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.