A trial to learn how camizestrant (AZD9833) works compared to fulvestrant and how safe it is in women with advanced breast cancer who have gone through menopause.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Apr 2020 → ongoing

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-504974-40-00

EudraCT number

2019-003706-27

ClinicalTrials.gov

NCT04214288

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Therapy, Pharmacogenomic, Efficacy, Pharmacogenetic, Pharmacokinetic

To determine the clinical efficacy (as assessed by PFS) of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer.

Secondary objectives 6

1. To evaluate the safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER positive HER2 negative breast cancer.
2. To determine anti-tumour effect of AZD9833 when compared to fulvestrant in women with advanced ER positive HER2 negative breast cancer.
3. To determine the effect of AZD9833 on survival and clinical benefit when compared to fulvestrant in women with advanced ER positive HER2 negative breast cancer.
4. To evaluate the PK of AZD9833 in this patient population at steady state.
5. To evaluate the pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients with advanced ER positive HER2-negative breast cancer.
6. To evaluate the effect of AZD9833 and fulvestrant on the patients' HRQoL, as assessed by patient completed HRQoL questionnaires.

Conditions and MedDRA coding

Estrogen Receptor Positive HER2 Negative Advanced Breast Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses. Patients are also required to consent to the provision of archival tumour biopsies.
2. For patients who consent, provision of signed and dated written informed consent prior to collection of sample for analysis.
3. Female patients aged at least 18 years.
4. Post-menopausal as per the defined criteria.
5. Histologically or cytological confirmation of adenocarcinoma of the breast.
6. ER-positive status of primary or metastatic tumour tissue.
7. HER2-negative
8. Metastatic disease or loco-regionally recurrent disease suitable for treatment with fulvestrant.
9. Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.
10. 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.
11. Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.Inclusion criterion for the paired tumour biopsy research subgroup.
12. Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.

Exclusion criteria 15

1. 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.
2. Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.
3. Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 and as specified in Appendix B of the protocol, prior to receiving the first dose of study treatment.
4. Drugs as indicated in Appendix B1 of the protocol.
5. Any cardiovascular criteria described in the protocol.
6. Radiotherapy with a limited field of radiation for palliation.
7. Major surgical procedure or significant traumatic injury.
8. Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system (CNS) metastatic disease.
9. Inadequate bone marrow reserve or organ function.
10. 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.
11. History of hypersensitivity to active or inactive excipients of AZD9833 or fulvestrant.
12. Previous randomisation in the present study.
13. Women of childbearing potential.
14. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
15. Patients with known active hepatitis (i.e. hepatitis B or C).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival

Secondary endpoints 9

1. Objective response rate
2. Duration of response
3. Percentage change in tumour size in tumour size at 16 weeks
4. Overall survival
5. Clinical benefit rate at 24 weeks
6. Plasma concentrations of AZD9833 and, if appropriate, metabolite(s)
7. Percent change from baseline in ER and progesterone receptor (PgR) expression assessed by the manual H-score method
8. Percent change from baseline in Ki67 labelling index.
9. Changes from baseline in total/subscale scores of the HrQoL questionnaires.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Third parties 1

Locations

7 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 64 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications