Clinical Trials /

A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

NCT04590248

Description:

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.

Related Conditions:
  • Endometrial Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Adavosertib as Treatment for Uterine Serous Carcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: D601HC00002
  • NCT ID: NCT04590248

Conditions

  • Uterine Serous Carcinoma

Interventions

DrugSynonymsArms
AdavosertibAZD1775Adavosertib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
AdavosertibExperimentalSubjects 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.
  • Adavosertib

Eligibility Criteria

        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.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description:The percentage of subjects with measurable disease at baseline who have a confirmed complete response (CR) or partial response (PR), as determined by Blinded Independent Central Review (BICR) per RECIST v1.1

Secondary Outcome Measures

Measure:Duration of response (DoR)
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description: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
Measure:Depth of response
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description:Absolute change and percentage change from baseline will be based on RECIST v1.1 target lesions measurements
Measure:Progression free survival (PFS)
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description:The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression), derived using RECIST v1.1 assessments based on BICR data
Measure:PFS6
Time Frame:From baseline up to 6 months
Safety Issue:
Description:The proportion of subjects alive and progression free at 6 months by Kaplan-Meier estimate
Measure:Overall survival (OS)
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description:The time from date of first dose until the date of death due to any cause
Measure:Disease control rate (DCR)
Time Frame:From baseline to approximately 24 months
Safety Issue:
Description:The percentage of subjects who have a best response of confirmed CR or PR or who have stable disease for at least 5 weeks after start of treatment, based on BICR data
Measure:Lowest concentration (Ctrough) of adavosertib
Time Frame:Pre-dose (60 minutes prior to dosing) on Day 5 of Cycles 1 and 2 (each cycle is 21 days)
Safety Issue:
Description:Lowest plasma concentration of adavosertib before next dose
Measure:Maximum concentration (Cmax) of adavosertib
Time Frame:2 hours post-dose on Day 5 of Cycles 1 and 2 (each cycle is 21 days)
Safety Issue:
Description:Maximum plasma concentration of adavosertib after oral dosing
Measure:Number of subjects with adverse events (AE) and serious AEs
Time Frame:From baseline to post-treatment follow-up (30 days after last dose)
Safety Issue:
Description:Assessment of AEs, vital signs, clinical laboratory values, electrocardiogram findings, and AEs leading to dose interruptions, dose reductions, and dose discontinuations

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Adavosertib
  • Phase 2b
  • open-label
  • single-arm

Last Updated

October 15, 2020