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A Phase 1 Study of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer

NCT04541433

Description:

This is a Phase 1, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD9833 in Japanese women with endocrineresistant ER+ HER2- breast cancer that is not amenable to treatment with curative intent. This study consists of 2 cohorts, Cohort1 and Cohort2. In cohort 1 (for tolerability evaluation), a minimum of 3, or up to 6, evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled. In cohort 2 (for exploratory research), at least 6 to maximum 12 evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer
  • Official Title: A Phase 1, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti- Tumor Activity of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: D8530C00006
  • NCT ID: NCT04541433

Conditions

  • ER+ HER2- Advanced Breast Cancer

Interventions

DrugSynonymsArms
AZD9833AZD9833 monotherapy

Purpose

This is a Phase 1, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD9833 in Japanese women with endocrineresistant ER+ HER2- breast cancer that is not amenable to treatment with curative intent. This study consists of 2 cohorts, Cohort1 and Cohort2. In cohort 1 (for tolerability evaluation), a minimum of 3, or up to 6, evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled. In cohort 2 (for exploratory research), at least 6 to maximum 12 evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled.

Detailed Description

      Objectives:

      Primary objective:

      To investigate the safety and tolerability of AZD9833 in Japanese women with ER+ HER2-
      advanced breast cancer

      Secondary objective:

      To assess the anti-tumor activity and efficacy of AZD9833

      Exploratory objectives:

      To investigate AZD9833 activity in tumor cells

      Overall design:

      This is a Phase 1, open-label study designed to evaluate the safety, tolerability,
      pharmacokinetics, and anti-tumor activity of AZD9833 in Japanese women with
      endocrineresistant ER+ HER2- breast cancer that is not amenable to treatment with curative
      intent. Eligible patients will receive AZD9833. In cohort 1 (for tolerability evaluation), a
      minimum of 3 to maximum 6 evaluable patients will be enrolled.

      For cohort 2, if paired biopsy after administration of the study drug becomes inoperable
      during administration of the study drug, additional subjects can be added to obtain an
      evaluable biopsy sample.

      In cohort 2 (for exploratory research), eligible patients will receive AZD9833 once daily and
      at least 6 to maximum 12 patients will be enrolled. In cohort 2, paired biopsy sample will be
      collected from at least 6 and maximum 12 patients. If paired biopsy after administration of
      the study drug becomes inoperable during administration of the study drug, additional
      subjects can be added to obtain an evaluable biopsy sample.

      Number of Subjects:

      Maximum 18 evaluable subjects will be enrolled in this study.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9833 monotherapyExperimentalDose escalation of AZD9833 monotherapy for patients with ER+ HER2- advanced breast cancer
  • AZD9833

Eligibility Criteria

        Major Inclusion Criteria:

          1. Signed written informed consent.

          2. >= 20 years.

          3. Any menopausal status:

             Pre and Post menopausal defined according to standard criteria in the protocol.

          4. Histological or cytological confirmation of adenocarcinoma of the breast.

          5. Documented positive estrogen receptor status of primary or metastatic tumor tissue,
             according to the local laboratory parameters. HER-2 negative.

          6. Metastatic or locoregionally recurrent disease and radiological or objective evidence
             of progression on or after the last systemic therapy prior to starting IMP.

          7. Prior chemotherapy, endocrine therapy and other therapy in the advanced setting is
             restricted as follows:

               1. No more than 2 lines of chemotherapy for advanced disease.

               2. Recurrence or progression on at least one line of endocrine therapy in the
                  advanced/metastatic disease setting.

               3. There is no limit on the number of lines of prior endocrine therapies.

               4. Prior treatment with CDK4/6 inhibitors is permitted.

          8. At least one lesion (measurable and/or non-measurable, as per RECIST 1.1) that can be
             accurately assessed at baseline and is suitable for repeated assessment by computed
             tomography (CT), magnetic resonance imaging (MRI), or plain X-ray; or clinical
             examination.

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

        Major Exclusion Criteria:

          1. Intervention with any of the following:

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

               2. Medications or herbal supplements known to be strong inhibitors/inducers of
                  cytochrome P450 (CYP) 3A4/5 sensitive CYP2B6 substrates and drugs which are
                  substrates of CYP2C9 and/or CYP2C19.

               3. Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.

               4. Radiotherapy with a limited field of radiation for palliation within one week of
                  the first dose of IMP, radiotherapy to more than 30% of the bone marrow or a wide
                  field of radiation within 4 weeks of the first dose of IMP.

               5. Major surgical procedure or significant traumatic injury.

          2. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
             starting IMP.

          3. Presence of life-threatening metastatic visceral disease.

          4. Evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses.

          5. 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.

          6. History of another primary malignancy.

          7. Male subjects are excluded from this study.

          8. History of hypersensitivity to active or inactive excipients of AZD9833.

          9. 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 <50%.

         10. Inadequate bone marrow reserve or organ function

         11. Involvement in the planning and conduct of the study.

         12. Judgment by the investigator that the patient should not participate in the study.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of subjects with dose-limiting toxicity, as defined in the protocol.
Time Frame:From the first dose of study treatment up to and including Cycle1 Day28.
Safety Issue:
Description:Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure:Duration of Response
Time Frame:At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure:Clinical benefit rate at 24 weeks
Time Frame:Up to 24 weeks
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure:Percentage Change in Tumour Size
Time Frame:At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure:Progression Free Survival
Time Frame:Up to objective disease progression or death (approximately 1 year).
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure:Maximum Observed Plasma Concentration (Cmax) of AZD9833
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks )
Safety Issue:
Description:Blood samples will be collected to assess plasma concentrations of AZD9833 at a series of timepoints to derive Cmax
Measure:Time to observed Cmax (Tmax) for AZD9833
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks )
Safety Issue:
Description:Blood samples will be collected to assess plasma concentrations of AZD9833 at a series of timepoints to derive Tmax

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer
  • Phase 1
  • Safety
  • Tolerability
  • Pharmacokinetics
  • ER Positive
  • HER2 Negative
  • Advanced Breast Cancer

Last Updated

April 8, 2021