AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma

NCT03668340 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-316
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying an investigational drug as a possible treatment for uterine cancer. The drug involved in this study is:

• AZD1775

Conditions

Uterine Cancer

Keywords

Uterine Cancer

Outcome Measures

Primary Outcomes (2)

• Objective response rate

  Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]

  2 years

• Progression-free survival

  Measured by the rate of progression-free survival at 6 months (PFS6) using RECIST v.1.1.

  6 months

Secondary Outcomes (3)

• Clinical benefit rate

  2 years

• Duration of Response

  2 years

• Assess the toxicities of AZD1775 in women with recurrent or persistent uterine serous carcinoma or uterine carcinosarcoma using CTCAE v4

  2 years

Study Arms (3)

Part A: AZD1775

EXPERIMENTAL

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Drug: AZD1775

Part B: AZD1775 in Carcinosarcoma

EXPERIMENTAL

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Drug: AZD1775

Part C: AZD1775 in Uterine Serous with biopsiable disease

EXPERIMENTAL

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Drug: AZD1775

Interventions

AZD1775 DRUG

AZD1775 blocks the activity of Wee1, a protein that helps to regulate how cells divide and grow. Certain cancer cells may be more vulnerable to having this process blocked

Part A: AZD1775; Part B: AZD1775 in Carcinosarcoma; Part C: AZD1775 in Uterine Serous with biopsiable disease

Eligibility Criteria

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

You may qualify if:

• Participants in Parts A and C 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 in Part B must have histologically or cytologically confirmed recurrent uterine carcinosarcoma. Additionally, the following features must also be present:
• Presence of a p53 alteration (by either IHC or next generation sequencing)
• Metastatic or extra-uterine component must be confirmed on pathology to be from the carcinoma component of the disease
• Patients without confirmation that the metastatic or extrauterine component of disease is of carcinoma histology may be considered after discussion with the PI
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured per RECIST 1.1 criteria. See Section 11 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 or uterine carcinosarcoma. 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.
• Age 18 years or older.
• ECOG performance status 0 or 1 (see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• hemoglobin ≥9 g/dL
• platelets ≥100,000/mcL
• total bilirubin ≤ 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 × ULN or ≤5 × ULN in patients with liver metastases

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 AZD1775, or those who have not recovered to Grade 1 from adverse events (excluding alopecia or anorexia) due to agents administered more than 3 weeks earlier. Participants may not have had hormonal therapy within 2 weeks of the first dose of AZD1775.
• Participants who are receiving any other investigational agents.
• Participants who have MSI-high or MMR-deficient tumors will not be eligible unless they have already received prior therapy with pembrolizumab or another PD1/PD-L1 immune checkpoint inhibitor or are deemed not to be a candidate for immune checkpoint therapy.
• Participants with known brain metastases or other CNS disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with treated brain metastases that have no evidence of progression or hemorrhage for at least 2 weeks after treatment will be allowed on study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD1775.
• Participants may not have had prior receipt of a cell cycle checkpoint inhibitor (e.g., Chek1, Wee1, or ATR inhibition)
• Participants receiving any medications or substances that are sensitive CYP3A4 substrates or are CYP3A4 substrates with a narrow therapeutic index, or which are moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior to Day 1 of dosing and withheld through the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant or fosaprepitant during this study is prohibited.
• Transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast cancer resistance protein (BRCP). Please see Appendix B for additional details regarding prohibited drugs and drugs to be used with caution, including drugs affected by CYP3A4 or BRCP. Because the lists of these agents are constantly changing, it is important to also regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information.
• 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 a percutaneous endoscopic gastrostomy (PEG) tube, be receiving total parenteral nutrition (TPN), or be dependent on IV fluid support.
• Participants with any of the following cardiac diseases currently or within the last 6 months as defined by the New York Heart Association (NYHA) ≥ Class 2 will not be eligible:
• Unstable angina pectoris
• Congestive heart failure
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Liu JF, Xiong N, Campos SM, Wright AA, Krasner C, Schumer S, Horowitz N, Veneris J, Tayob N, Morrissey S, West G, Quinn R, Matulonis UA, Konstantinopoulos PA. Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma. J Clin Oncol. 2021 May 10;39(14):1531-1539. doi: 10.1200/JCO.20.03167. Epub 2021 Mar 11.

  PMID: 33705205 DERIVED

MeSH Terms

Conditions

Uterine Neoplasms

Interventions

adavosertib

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

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 12, 2018
• Study Start: October 22, 2018
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)