A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

NCT ID: NCT04590248

Last Updated: 2023-08-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

109 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-30

Study Completion Date

2023-02-07

Brief Summary

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This Phase 2b study aims to evaluate the efficacy and safety of adavosertib, an inhibitor of the tyrosine kinase WEE1, in subjects with recurrent or persistent uterine serous carcinoma (USC) who have previously received at least 1 prior platinum-based chemotherapy regimen for the management of USC.

Detailed Description

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This Phase 2b, open-label, single-arm, multi-center study will assess the efficacy and safety of adavosertib in eligible subjects with histologically confirmed recurrent or persistent USC, evidence of measurable disease as per Response Evaluation Criteria in Solid Tumors.(RECIST) v1.1, and who have received at least 1 prior platinum-based chemotherapy regimen for the management of USC. Subjects with carcinosarcomas are not eligible.

Conditions

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Uterine Serous Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Adavosertib

Subjects will receive adavosertib 300 mg administered orally, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.

Group Type EXPERIMENTAL

Adavosertib

Intervention Type DRUG

The subjects will receive oral adavosertib 300 mg, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.

Interventions

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Adavosertib

The subjects will receive oral adavosertib 300 mg, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.

Intervention Type DRUG

Other Intervention Names

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AZD1775

Eligibility Criteria

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Inclusion Criteria

1. Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed consent.
2. Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.
3. Evidence of measurable disease as per RECIST v1.1.
4. At least 1 prior platinum-based chemotherapy regimen for the management of USC. Prior receipt of immune checkpoint inhibitors, vascular endothelial growth factor (VEGF) inhibitors and human epidermal growth factor receptor 2 (HER2) targeted therapy is allowed. There is no restriction on the number of prior lines of systemic therapy.
5. Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
6. Life expectancy ≥ 12 weeks.
7. Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
8. Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.
9. Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.

Exclusion Criteria

1. Any underlying medical condition and uncontrolled intercurrent illness that would impair the ability of the subject to receive study treatment, as judged by the investigator.
2. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment.
3. Unable to swallow oral medications.
4. Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
5. Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
6. Any of the following cardiac diseases currently or within the last 6 months:

* Unstable angina pectoris
* Acute myocardial infarction
* Congestive heart failure
* Conduction abnormality not controlled with pacemaker or medication
* Significant ventricular or supraventricular arrhythmias
7. History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
8. a) Resting corrected QTc interval using the Fridericia formula (QTcF) \> 480 msec, or b) congenital long QT syndrome.
9. Immunocompromised subjects.
10. Subjects with known active hepatitis (ie, hepatitis B or C).
11. Prior treatment with any of the following:

* Cell cycle checkpoint inhibitor.
* Anticancer treatment drug ≤ 21 days (≤ 6 weeks for nitrosoureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib. For Programmed cell death-1 receptor (PD-1) /Programmed death-ligand 1 (PD-L1) inhibitors, a minimum of 28 days since last dose is required.
* Prescription or non-prescription drugs known as moderate to strong inhibitors / inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment.
* Herbal medications 7 days prior to first dose of study treatment.
12. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation within 4 weeks prior to the first dose of study intervention.
13. Major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, prior to beginning study.
14. Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.
15. Currently pregnant or breast-feeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joyce Liu, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Research Site

Burbank, California, United States

Site Status

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Duarte, California, United States

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La Jolla, California, United States

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West Hollywood, California, United States

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Aurora, Colorado, United States

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Iowa City, Iowa, United States

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Covington, Louisiana, United States

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Boston, Massachusetts, United States

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Rochester, Minnesota, United States

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New Brunswick, New Jersey, United States

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New York, New York, United States

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The Bronx, New York, United States

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Spokane, Washington, United States

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Vancouver, Washington, United States

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Toronto, , Canada

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Dijon, , France

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Marseille, , France

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Nice, , France

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Pierre-Bénite, , France

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Saint-Herblain, , France

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Milan, , Italy

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Napoli, , Italy

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Roma, , Italy

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A Coruña, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Pozuelo de Alarcón, , Spain

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Countries

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United States Canada France Italy Spain

References

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Liu JF, Colombo N, Oza AM, Frenel JS, Corr BR, Rubinstein MM, Nevadunsky NS, Lheureux S, Gaba L, Gonzalez Cortijo L, Salutari V, You B, Chiang S, O'Connor MJ, Oplustil O'Connor L, Meulendijks D, Khatun M, Ghiorghiu D, Oaknin A. ADAGIO: A Phase IIb, Open-Label, Single-Arm, Multicenter Study Assessing the Efficacy and Safety of Adavosertib (AZD1775) as Treatment for Recurrent or Persistent Uterine Serous Carcinoma. J Clin Oncol. 2025 Sep 10;43(26):2897-2907. doi: 10.1200/JCO-24-01606. Epub 2025 Apr 22.

Reference Type DERIVED
PMID: 40262070 (View on PubMed)

Liu J, Oza AM, Colombo N, Oaknin A. ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma. Int J Gynecol Cancer. 2022 Jan;32(1):89-92. doi: 10.1136/ijgc-2021-003144. Epub 2021 Oct 29.

Reference Type DERIVED
PMID: 34716177 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D601HC00002

Identifier Type: -

Identifier Source: org_study_id

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