Clinical Trials /

A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer

NCT04588298

Description:

This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics (PK) of different doses of oral AZD9833 in post-menopausal (and potentially pre-menopausal)women with primary breast cancer.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer
  • Official Title: A Randomised, Open-Label, Parallel-Group, Pre-surgical Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2-negative Primary Breast Cancer (SERENA-3)

Clinical Trial IDs

  • ORG STUDY ID: D8530C00003
  • SECONDARY ID: 2020-001079-33
  • NCT ID: NCT04588298

Conditions

  • HER2-negative Breast Cancer

Interventions

DrugSynonymsArms
AZD9833AZD9833 Dose A
FulvestrantFulvestrant 500 mg (Optional)

Purpose

This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics (PK) of different doses of oral AZD9833 in post-menopausal (and potentially pre-menopausal)women with primary breast cancer.

Detailed Description

      The study will be conducted in approximately 20 study centers across 3 countries and will be
      conducted in two stages (stage 1 and stage 2). After the screening visit and confirmation of
      eligibility, evaluable participants will be enrolled across treatment groups. In stage 1, up
      to 24 evaluable participants across two treatment groups will be enrolled. A Safety and Data
      Monitoring Committee will convene to review stage 1 data and decide whether further treatment
      groups are required in stage 2. Stage 2 may include up to 60 evaluable participants across up
      to 5 treatment groups.

      Stage 1 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily

      Stage 2 (Optional) Group 1: AZD9833 Dose C once daily Group 2: AZD9833 Dose D once daily
      Group 3: AZD9833 Dose E once daily Group 4: Fulvestrant 500 mg Group 5: AZD9833 Dose F once
      daily (pre-menopausal women)

      AZD9833 doses C, D, E or F could be the same as Dose A or Dose B from stage 1.

      Adverse events and concomitant medications information will be collected throughout the
      study. Thereafter there will be 28-day follow-up visit after discontinuation of study
      treatment.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9833 Dose AExperimentalPost-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.
  • AZD9833
AZD9833 Dose BExperimentalPost-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.
  • AZD9833
AZD9833 Dose C (Optional)ExperimentalPost-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.
  • AZD9833
AZD9833 Dose D (Optional)ExperimentalPost-menopausal participants will receive once daily oral dose D of AZD9833 in stage 2 of the study.
  • AZD9833
AZD9833 Dose E (Optional)ExperimentalPost-menopausal participants will receive once daily oral dose E of AZD9833 in stage 2 of the study.
  • AZD9833
AZD9833 Dose F (Optional)ExperimentalPre-menopausal participants will receive once daily oral dose F of AZD9833 in stage 2 of the study.
  • AZD9833
Fulvestrant 500 mg (Optional)ExperimentalPost-menopausal participants will receive intramuscular (IM) injection of fulvestrant 500 mg in stage 2 of the study.
  • Fulvestrant

Eligibility Criteria

        Inclusion criteria:

          -  Provision of written informed consent prior to study entry

          -  Female participants aged at least 18 years

          -  Post-menopausal status defined as meeting at least one of the following criteria:

               1. Have undergone a bilateral oophorectomy

               2. Age ≥ 60 years

               3. Age ≥ 50 and < 60 years and with cessation of menses ≥ 12 months and
                  follicle-stimulating hormone and oestradiol levels in the post-menopausal range
                  and with an intact uterus in the absence of oral contraception or hormone
                  replacement therapy prior to the diagnosis of breast cancer

          -  Pre-menopausal status (Stage 2 only) defined as participants who are naturally
             pre-menopausal (i.e. without concurrent ovarian suppression)

             (a) Women of childbearing potential must: (i) Not be breastfeeding (ii) Have a
             negative pregnancy test prior to the start of dosing (iii) Agree to use one highly
             effective barrier method of contraception from the time of screening until 4 weeks
             after discontinuing study treatment

          -  Female participants with newly diagnosed primary breast cancer scheduled to undergo
             treatment with curative intent by surgery and irrespective of clinical node status

          -  Histologically confirmed invasive breast cancer involving a palpable tumour of any
             size, or a tumour with an ultrasound assessed diameter of ≥ 1.0 cm

          -  Participants with adequately treated non-melanoma skin cancer, curatively treated
             in-situ cancer of the cervix, or other solid tumours curatively treated with no
             evidence of disease for ≥ 3 months can be considered for the study

          -  According to the local laboratory participants must have:

               1. ER positive breast cancer

               2. HER2-negative breast cancer

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

        Exclusion Criteria:

          -  Previous systemic or local treatment for the new primary breast cancer currently under
             investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)

          -  Intervention with any of the following:

               1. Use of sex-hormone-containing drugs within 6 months prior to the first dose of
                  study treatment

               2. Medications or herbal supplements known to be strong inhibitors/inducers of
                  CYP3A4/5, sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9
                  and/or CYP2C19 which have a narrow therapeutic index

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

          -  Inflammatory breast cancer

          -  Any evidence of severe or uncontrolled systemic diseases which in the investigator's
             opinion makes it undesirable for the participant to participate in the study

          -  Any of the following cardiovascular criteria: Mean resting QTcF > 470 msec; resting
             heart rate of < 50 bpm; any clinically important abnormalities in rhythm, conduction,
             or morphology of resting ECG; any factors that increase the risk of QTc prolongation
             or risk of arrhythmic events; known left ventricular ejection fraction < 50%;
             significant cardiovascular procedure or event within the last 6 months; uncontrolled
             hypertension or symptomatic hypotension

          -  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 (stage 2 only)

          -  Previous randomisation in the present study

          -  Judgement by the Investigator that the participant should not participate in the study
             if the participant is unlikely to comply with study procedures, restrictions and
             requirements
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change from baseline in estrogen receptor (ER) expression between pre- and on-treatment tumour samples measured by immunohistochemistry (IHC)
Time Frame:Baseline (Screening Day -21 to 1) and Days 5 to 7
Safety Issue:
Description:To explore the ER pharmacodynamic (PD) effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 treatment.

Secondary Outcome Measures

Measure:Change from baseline in progesterone receptor (PgR) expression between pre- and on-treatment tumour samples measured by IHC
Time Frame:Baseline (Screening Day -21 to 1) and Days 5 to 7
Safety Issue:
Description:To explore the PgR PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 and fulvestrant treatment (if applicable).
Measure:Change from baseline in Ki-67 labelling index between pre- and on-treatment tumour samples measured by IHC
Time Frame:Baseline (Screening Day -21 to 1) and Days 5 to 7
Safety Issue:
Description:To explore the Ki-67 PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 and fulvestrant treatment (if applicable).
Measure:Number of adverse events (AEs) experienced by participants
Time Frame:From screening (Day -21 to 1) through 28-day follow-up (Upto 2 months)
Safety Issue:
Description:Safety and tolerability will be assessed through the incidence of AEs.
Measure:Plasma concentrations of AZD9833 on the biopsy day
Time Frame:Days 5 to 7
Safety Issue:
Description:To evaluate the PK of AZD9833 in this participant population.

Details

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

Trial Keywords

  • Breast cancer
  • Breast carcinoma
  • Estrogen-Receptor-positive breast cancer
  • HER2-negative breast cancer

Last Updated

October 8, 2020