Clinical Trials /

A Comparative Study of AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer

NCT04214288

Description:

This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Comparative Study of AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer
  • Official Title: SERENA-2: A Randomised, Open-Label, Parallel-Group, Multicentre Phase 2 Study Comparing the Efficacy and Safety of Oral AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: D8530C00002
  • NCT ID: NCT04214288

Conditions

  • Advanced ER-Positive HER2-Negative Breast Cancer

Interventions

DrugSynonymsArms
AZD9833AZD9833 Dose A
FulvestrantFulvestrant 500 mg

Purpose

This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.

Detailed Description

      Post-menopausal women with histologically or cytologically confirmed metastatic or
      loco-regionally recurrent ER-positive HER2-negative breast cancer before randomization and
      fulfilling all of the inclusion criteria and none of the exclusion criteria will be included.

      After the screening visit and confirmation of eligibility, patients will be randomly assigned
      in a 1:1:1:1 ratio to receive 1 of the following 4 treatments, consisting of 4-week treatment
      cycles until disease progression (assessed by the Investigator as defined by Response
      Evaluation Criteria in Solid Tumours [RECIST] version 1.1):

        -  AZD9833 (Dose A)

        -  AZD9833 (Dose B)

        -  AZD9833 (Dose C)

        -  Fulvestrant (500 mg) During the treatment period, patients will have scheduled visits
           until treatment discontinuation.

      After the end of treatment, patients will attend 2 safety follow-up visits (at the time of
      treatment discontinuation and 28 days later) and will continue to be followed for survival.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9833 Dose AExperimentalThe patients will receive AZD9833 (Dose A).
  • AZD9833
AZD9833 Dose BExperimentalThe patients will receive AZD9833 (Dose B).
  • AZD9833
AZD9833 Dose CExperimentalThe patients will receive AZD9833 (Dose C).
  • AZD9833
Fulvestrant 500 mgActive ComparatorThe patients will receive Fulvestrant (500 mg).
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Post-menopausal female patients aged at least 18 years.

          -  Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of
             the breast.

          -  Radiological or other objective evidence of progression on or after the last systemic
             therapy prior to starting study treatment.

          -  Patients must have at least 1 lesion, not previously irradiated, that can be measured
             accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable
             disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.

          -  Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance
             status 0 to 1.

          -  Prior endocrine therapy as follows:

               1. Recurrence or progression on at least one line of endocrine therapy

               2. No more than 1 line of endocrine therapy for advanced disease

               3. No more than 1 line of chemotherapy for advanced disease

               4. Prior treatment with CDK4/6 inhibitors is permitted

               5. No prior treatment with fulvestrant, oral selective oestrogen receptor degrader
                  (SERD), or related therapies

          -  Inclusion criterion for the paired tumour biopsy research subgroup:

        Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose
        on-study biopsy.

        Exclusion Criteria:

        Intervention with any of the following:

          -  Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the
             treatment of breast cancer from a previous treatment regimen or clinical study within
             14 days of the first dose of study treatment.

          -  Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior
             to the first dose of study treatment.

          -  Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome
             P450 3A4/5 and sensitive CYP2B6 substrates.

          -  Drugs that are known to prolong QT and have a known risk of torsades de pointes.

          -  The following cardiovascular criteria: QTcF >470 ms, resting heart rate <45 bpm,
             clinically significant abnormalities of resting electrocardiogram, uncontrolled
             hypertension, symptomatic hypotension, factors that increase the risk for QTc
             prolongation, left ventricular ejection fraction <40%

          -  Radiotherapy with a limited field of radiation for palliation within 1 week of dosing,
             or to > 30% of bone marrow or a wide field within 4 weeks of dosing.

          -  Major surgical procedure or significant traumatic injury.

          -  Presence of life-threatening metastatic visceral disease or uncontrolled central
             nervous system metastatic disease.

          -  Inadequate bone marrow reserve or organ function.

          -  Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases,
             inability to swallow the formulated product, or previous significant bowel resection
             that would preclude adequate absorption of AZD9833.

          -  History of hypersensitivity to active or inactive excipients of AZD9833 or
             fulvestrant.

          -  Previous randomisation in the present study.

          -  Women of childbearing potential.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1
Time Frame:From date of randomisation to date of objective disease progression or death (up to approximately 3 years)
Safety Issue:
Description:Time from randomisation to objective disease progression (as assessed by RECIST) or death.

Secondary Outcome Measures

Measure:Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1
Time Frame:From screening until disease progression (up to approximately 3 years)
Safety Issue:
Description:The ORR is defined as the percentage of patients with at least 1 Investigator-assessed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression.
Measure:Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1
Time Frame:From screening until disease progression (up to approximately 3 years)
Safety Issue:
Description:The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Measure:Percentage change in tumour size at 16 weeks
Time Frame:At Week 16
Safety Issue:
Description:Percentage change in the sum of longest target lesions diameters at 16 weeks.
Measure:Overall survival (OS)
Time Frame:From the date of randomisation until death (up to approximately 3 years)
Safety Issue:
Description:The OS is defined as the time from randomisation to death due to any cause.
Measure:Clinical benefit rate at 24 weeks (CBR24)
Time Frame:At Week 24
Safety Issue:
Description:Percentage of patients with CBR (defined as best objective response of CR, PR or stable disease [SD] at 24 weeks).
Measure:Plasma concentrations of AZD9833 and, if appropriate, metabolite(s)
Time Frame:Cycle 1 Day 15 (pre- and post-dose) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)
Safety Issue:
Description:To evaluate the pharmacokinetic (PK) profile of AZD9833 in this patient population at steady state.
Measure:Percent change from baseline in ER and PgR expression and Ki67 labelling index.
Time Frame:From baseline to Cycle 2 Day 1 (each cycle is 28 days in length).
Safety Issue:
Description:The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.
Measure:Changes from baseline in Health Related Quality of Life (HRQoL)
Time Frame:From Day 1 until end of treatment and safety follow up (up to approximately 3 years)
Safety Issue:
Description:To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.

Details

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

Trial Keywords

  • Open-Label
  • Parallel-Group
  • Fulvestrant
  • ER-Positive HER2-Negative Breast Cancer
  • Metastatic
  • AZD9833
  • Oral SERD

Last Updated

December 27, 2019