Uterine Serous CarcinomaPhase 2ADAGIONCT04590248
A Study of Adavosertib as Treatment for Uterine Serous Carcinoma
A Phase 2 study testing Adavosertib in people with Uterine Serous Carcinoma, run by AstraZeneca at 27 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Uterine Serous Carcinoma
- What is being tested?
- Adavosertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 27 sitesin 5 countries
- Study dates
- 30 Nov 2020to 7 Feb 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed consent.
- Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.
- Evidence of measurable disease as per RECIST v1.1.
- 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.
- Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
- Life expectancy ≥ 12 weeks.
Show all 9Show fewer
- Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
- Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.
- Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.
Who cannot join
- 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.
- 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.
- Unable to swallow oral medications.
- Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
- Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
- Any of the following cardiac diseases currently or within the last 6 months:
Show all 24Show fewer
- Unstable angina pectoris
- Acute myocardial infarction
- Congestive heart failure
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias
- History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
- a) Resting corrected QTc interval using the Fridericia formula (QTcF) > 480 msec, or b) congenital long QT syndrome.
- Immunocompromised subjects.
- Subjects with known active hepatitis (ie, hepatitis B or C).
- 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.
- 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.
- Major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, prior to beginning study.
- Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.
- Currently pregnant or breast-feeding.
Trial locations and contacts
27 sites in 5 countries.
27 sites in 5 countries
United States14 sites
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02215
Research Site
Burbank, California, 91505
Research Site
Covington, Louisiana, 70433
Research Site
Duarte, California, 91010
Research Site
Iowa City, Iowa, 52242
Research Site
La Jolla, California, 92093
Research Site
New Brunswick, New Jersey, 08903
Research Site
New York, New York, 10065
Research Site
Rochester, Minnesota, 55905
Research Site
Spokane, Washington, 99202
Research Site
The Bronx, New York, 10467
Research Site
Vancouver, Washington, 98684
Research Site
West Hollywood, California, 90048
France5 sites
Research Site
Dijon, 21079
Research Site
Marseille, 13273
Research Site
Nice, 6189
Research Site
Pierre-Bénite, 69495
Research Site
Saint-Herblain, 44805
Spain4 sites
Research Site
A Coruña, 15009
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Pozuelo de Alarcón, 28223
Italy3 sites
Research Site
Milan, 20141
Research Site
Naples, 80131
Research Site
Roma, 00168
About this study
Official title: A Phase 2b, Open-label, Single-arm, Multi-centre Study Assessing the Efficacy and Safety of Adavosertib as Treatment for Recurrent or Persistent Uterine Serous Carcinoma
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.
Read the detailed description
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
- Uterine Serous Carcinoma
- Being tested
- Adavosertib
- Keywords
- Adavosertib, Phase 2b, open-label, single-arm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdavosertibDrug
Also called AZD1775
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.
| Study group | Role | What they receive |
|---|---|---|
| Adavosertib | Experimental | 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. Receives: Drug: Adavosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 for target lesions (TLs) and assessed by computed tomography (CT) or magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions; Partial response (PR), >=30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Measured: up to 75 weeks
Secondary outcomes (9)
Duration of Response (DoR)
The time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death in the absence of disease progression
Measured: up to 75 weeks
Depth of Response
Depth of response is defined as best percentage change from baseline in target lesion size, which is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. A negative change denotes a reduction in target lesion size.
Measured: Up to 75 weeks
Progression Free Survival (PFS)
The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from study drug or receives another anticancer therapy prior to progression. PFS was assessed per RECIST v1.1 using CT or MRI scans by BICR.
Measured: Up to 75 weeks
Progression Free Survival Rate at 6 Months (PFS6)
The progression free survival rate was assessed at 6 months by Kaplan-Meier estimate per RECIST v1.1.
Measured: Up to 6 months
Overall Survival (OS)
The time from date of first dose until the date of death due to any cause
Measured: Up to 75 weeks
Disease Control Rate (DCR)
The percentage of participants who have a best overall response of confirmed response (CR) or partial response (PR) or who have stable disease for at least 5 weeks after start of treatment, based on BICR.
Measured: Up to 75 weeks
Lowest Concentration (Ctrough) of Adavosertib
Lowest plasma concentration of adavosertib was evaluated as pharmacokinetic paramerter.
Measured: Cycle 1, Day 5 and Cycle 2, Day 5 (pre-dose) (each cycle is 21 days)
Maximum Concentration (Cmax) of Adavosertib
Maximum plasma concentration of adavosertib was evaluated as pharmacokinetic parameter.
Measured: Cycle 1, Day 5 and Cycle 2, Day 5 (2 hours post-dose) (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (AEs)
The number of participants with treatment emergent adverse events (AEs) were assessed as variable of safety and tolerability. The adverse events reported here were treatment emergent.
Measured: From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start30 Nov 2020
- Primary completion23 May 2022
- Study completion7 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Uterine Serous CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Joyce Liu, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04590248
- Sponsor's protocol ID
- D601HC00002
- Acronym
- ADAGIO
- Status last verified
- Aug 2023
- First submitted
- 22 Sep 2020
- Last updated
- 14 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
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.
PubMed 40262070Liu 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.
PubMed 34716177
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b, Open-label, Single-arm, Multi-centre Study Assessing the Efficacy and Safety of Adavosertib as Treatment for Recurrent or Persistent Uterine Serous Carcinoma
- ClinicalTrials.gov ID
- NCT04590248
- Acronym / sponsor ID
- ADAGIO / D601HC00002
- Conditions
- Uterine Serous Carcinoma
- Keywords
- Adavosertib, Phase 2b, open-label, single-arm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 23 May 2022 (actual)
- Study completion
- 7 Feb 2023 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adavosertib | Experimental | Drug: AdavosertibSubjects 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed consent.
- Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.
- Evidence of measurable disease as per RECIST v1.1.
- 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.
- Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
Key exclusion criteria (24 listed)
- 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.
- 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.
- Unable to swallow oral medications.
- Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
- Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdavosertibAlso: AZD1775The 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. | Drug | Adavosertib |
Primary outcome
Objective Response Rate (ORR)
Time frame: up to 75 weeks
Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 for target lesions (TLs) and assessed by computed tomography (CT) or magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions; Partial response (PR), >=30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
9 secondary outcomes
Duration of Response (DoR)
Time frame: up to 75 weeks
Depth of Response
Time frame: Up to 75 weeks
Progression Free Survival (PFS)
Time frame: Up to 75 weeks
Progression Free Survival Rate at 6 Months (PFS6)
Time frame: Up to 6 months
Overall Survival (OS)
Time frame: Up to 75 weeks
Disease Control Rate (DCR)
Time frame: Up to 75 weeks
Lowest Concentration (Ctrough) of Adavosertib
Time frame: Cycle 1, Day 5 and Cycle 2, Day 5 (pre-dose) (each cycle is 21 days)
Maximum Concentration (Cmax) of Adavosertib
Time frame: Cycle 1, Day 5 and Cycle 2, Day 5 (2 hours post-dose) (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time frame: From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40262070Liu 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.
- Derived from this study: PubMed 34716177Liu 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.
- D601HC00002\_CSR\_Synopsis\_redactedLink provided by the sponsor.
- Statistical Analysis Plan (SAP)Link provided by the sponsor.
- CSPLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for Uterine Serous Carcinoma
RecruitingPhase 1/2
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer
RecruitingPhase 1
Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer
Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma
Active, not recruitingPhase 2
Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
Endometrial Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma
Active, not recruitingPhase 3
Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma
RecruitingPhase 2
Study of EV for Recurrent Endometrial Carcinoma
Endometrial Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joyce Liu, MD, MPH principal investigator
Dana-Farber Cancer Institute
27 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adavosertib in people with Uterine Serous Carcinoma, run by AstraZeneca at 27 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, France, Spain, Italy, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 75 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04590248, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.