Clinical Trials /

Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer

NCT03616587

Description:

A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Women with ER Positive, HER2 Negative Advanced Breast Cancer (SERENA-1)

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer
  • Official Title: A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Women With ER-positive, HER2-negative Advanced Breast Cancer (SERENA-1)

Clinical Trial IDs

  • ORG STUDY ID: D8530C00001
  • SECONDARY ID: 2018-000667-92
  • SECONDARY ID: 138396
  • NCT ID: NCT03616587

Conditions

  • ER+ HER2- Advanced Breast Cancer

Interventions

DrugSynonymsArms
AZD9833AZD9833 monotherapy dose escalation
AZD9833 with palbociclibAZD9833 with palbociclib dose escalation
AZD9833AZD9833 monotherapy dose expansion
AZD9833 with palbociclibAZD9833 with palbociclib dose expansion
AZD9833 with everolimusAZD9833 with everolimus dose escalation
AZD9833 with everolimusAZD9833 with everolimus dose expansion
AZD9833 with abemaciclib dose escalationAZD9833 with abemaciclib dose escalation
AZD9833 with abemaciclibAZD9833 with abemaciclib dose expansion

Purpose

A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Women with ER Positive, HER2 Negative Advanced Breast Cancer (SERENA-1)

Detailed Description

      This is a multicentre dose escalation and expansion, first-in-human study designed to
      evaluate the safety and tolerability of AZD9833, alone (Parts A and B) or in combination with
      palbociclib (Parts C and D) or in combination with everolimus (Parts E and F) or in
      combination with abemaciclib (Parts G and H), in women with endocrine-resistant ER+ HER2-
      breast cancer that is not amenable to treatment with curative intent.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9833 monotherapy dose escalationExperimental
  • AZD9833
AZD9833 monotherapy dose expansionExperimental
  • AZD9833
AZD9833 with palbociclib dose escalationExperimental
  • AZD9833 with palbociclib
AZD9833 with palbociclib dose expansionExperimental
  • AZD9833 with palbociclib
AZD9833 with everolimus dose expansionExperimental
  • AZD9833 with everolimus
AZD9833 with everolimus dose escalationExperimental
  • AZD9833 with everolimus
AZD9833 with abemaciclib dose escalationExperimental
  • AZD9833 with abemaciclib dose escalation
AZD9833 with abemaciclib dose expansionExperimental
  • AZD9833 with abemaciclib

Eligibility Criteria

        Inclusion

          1. Signed written informed consent

          2. >= 18 years

          3. Any menopausal status:

               1. Pre-menopausal women must have commenced treatment with an LHRH agonist at

                  least 4 weeks prior to starting IMP (AZD9833 ± palbociclib, everolimus or
                  abemaciclib) and must be willing to continue to receive LHRH agonist therapy for
                  the duration of the study

               2. Post-menopausal defined according to standard criteria in the protocol

          4. Histological or cytological confirmation of adenocarcinoma of the breast

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

          6. Metastatic disease or locoregionally recurrent disease which is refractory or
             intolerant to existing therapy(ies) known to provide clinical benefit

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

          8. Prior chemotherapy, endocrine therapy and other therapy 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

          9. Women of childbearing potential must agree to use a highly effective contraceptive
             measure, must not be breast feeding, and must have a negative pregnancy test prior to
             the start of dosing

         10. 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 CT, MRI, or
             plain X-ray; or clinical examination. Blastic-only lesions in bone are not considered
             assessable

         11. ECOG/ WHO performance status 0 to 1, with no deterioration over the previous 2 weeks
             and a minimum life expectancy of 12 weeks

             Inclusion criteria for the paired tumour biopsy research:

         12. Disease suitable for paired baseline and on-study tumour biopsies

         13. Washout from prior fulvestrant: 6 months

         14. Washout from prior tamoxifen: 4 months

         15. Signed written informed consent for tumour biopsies
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 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:Minimum observation period 28 days on treatment.
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:Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) 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:Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) 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:Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) 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:Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) 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:Maximum Observed Plasma Concentration (Cmax) of AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Safety Issue:
Description:Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib at a series of timepoints to derive Cmax
Measure:Time to observed Cmax (Tmax) for AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Safety Issue:
Description:Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib at a series of timepoints to derive Tmax
Measure:Area under the plasma concentration-time curve (AUC) for AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Safety Issue:
Description:Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus or Abemaciclib at a series of timepoints to derive AUC
Measure:Renal clearance (CLR) for AZD9833
Time Frame:At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Safety Issue:
Description:Urine samples will be collected to assess urine concentrations of AZD9833 at a series of timepoints to derive renal clearance
Measure:Assessment of biomarker changes
Time Frame:At pre-defined time intervals throughout the AZD9833 treatment period and at discontinuation. (approximately1 year)
Safety Issue:
Description:Blood samples will be collected to assess biomarker changes of estrogen receptor (ER), progesterone receptor (PgR) and Ki67 protein at a series of timepoints to derive AZD9833 activity in tumour cells.

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
  • Camizestrant

Last Updated

March 22, 2021