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A Comparative Study of AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer (SERENA-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04214288
Recruitment Status : Recruiting
First Posted : January 2, 2020
Last Update Posted : November 30, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced ER-Positive HER2-Negative Breast Cancer Drug: AZD9833 Drug: Fulvestrant Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 22, 2020
Estimated Primary Completion Date : March 23, 2022
Estimated Study Completion Date : December 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: AZD9833 Dose A
The patients will receive AZD9833 (Dose A).
Drug: AZD9833
Dosage formulation: AZD9833 tablets will be administered orally.

Experimental: AZD9833 Dose B
The patients will receive AZD9833 (Dose B).
Drug: AZD9833
Dosage formulation: AZD9833 tablets will be administered orally.

Experimental: AZD9833 Dose C
The patients will receive AZD9833 (Dose C).
Drug: AZD9833
Dosage formulation: AZD9833 tablets will be administered orally.

Active Comparator: Fulvestrant 500 mg
The patients will receive Fulvestrant (500 mg).
Drug: Fulvestrant
Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.




Primary Outcome Measures :
  1. 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) ]
    Time from randomisation to objective disease progression (as assessed by RECIST) or death.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. Percentage change in tumour size at 16 weeks [ Time Frame: At Week 16 ]
    Percentage change in the sum of longest target lesions diameters at 16 weeks.

  4. Overall survival (OS) [ Time Frame: From the date of randomisation until death (up to approximately 3 years) ]
    The OS is defined as the time from randomisation to death due to any cause.

  5. Clinical benefit rate at 24 weeks (CBR24) [ Time Frame: At Week 24 ]
    Percentage of patients with CBR (defined as best objective response of CR, PR or stable disease [SD] at 24 weeks).

  6. 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) ]
    To evaluate the pharmacokinetic (PK) profile of AZD9833 in this patient population at steady state.

  7. 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). ]
    The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.

  8. 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) ]
    To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.
  • 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 <50%.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04214288


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04214288    
Other Study ID Numbers: D8530C00002
First Posted: January 2, 2020    Key Record Dates
Last Update Posted: November 30, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Access Criteria:

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Open-Label
Parallel-Group
Fulvestrant
ER-Positive HER2-Negative Breast Cancer
Metastatic
AZD9833
Oral SERD
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs