An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Mar 2024 → ongoing

Decision date (initial)

2024-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

External identifiers

EU CT number

2023-504031-41-00

ClinicalTrials.gov

NCT05952557

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety, Pharmacogenomic

To demonstrate superiority of camizestrant ± abemaciclib as compared to standard endocrine therapy ± abemaciclib in preventing breast cancer recurrence

Secondary objectives 4

1. To evaluate the efficacy of camizestrant ± abemaciclib as compared to standard endocrine therapy ± abemaciclib in terms of overall survival and other measures
2. To evaluate the safety of camizestrant ± abemaciclib as compared to standard endocrine therapy ± abemaciclib compared to with standard endocrine therapy
3. To characterize the camizestrant pharmacokinetics (PK)
4. To assess patient-reported treatment associated symptoms and quality of life in patients treated with camizestrant ± abemaciclib as compared to standard endocrine therapy ± abemaciclib

Conditions and MedDRA coding

ER+/HER2- Early Breast Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD 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 Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the deidentified 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Women and Men; ≥18 years at the time of screening (or per national guidelines)
2. Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with absence of any evidence of metastatic disease as defined in the protocol
3. Completed adequate (definitive) locoregional therapy (surgery with or without radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant chemotherapy. Patients must be randomised within 12 months of definitive breast surgery. Patients may have received up to 12 weeks of endocrine therapy either in the adjuvant orneoadjuvant setting prior to randomisation
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Adequate organ and marrow function

Exclusion criteria 14

1. Inoperable locally advanced or metastatic breast cancer
2. Known LVEF <50% with heart failure NYHA Grade ≥2
3. Mean resting QTcF interval > 480 ms at screening
4. Concurrent exogenous reproductive hormone therapy or non topical hormonal therapy for non-cancer-related conditions
5. SUB-STUDY ONLY: Initiation of restricted medications prior to randomisation in main study. Patients assessed as not able to comply with study procedures, restrictions, and requirements
6. SUB-STUDY ONLY: Comorbidities or concomitant medications; ongoing skin conditions, bleeding of unknown aetiology that might impact assessment of sub-study objectives.
7. Any concurrent anti-cancer treatment not specified in the protocol with the exception of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors ( eg, denosumab)
8. Previous treatment with camizestrant, investigational SERDs/investigational ER targeting agents, or fulvestrant
9. For PORTUGAL ONLY: Patients with known germline or somatic BRCA1/2 mutations.
10. Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding
11. Patients with known hypersensitivity to active or inactive excipients of camizestrant or drugs with a similar chemical structure or class to camizestrant. In pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance to LHRH agonists that would preclude the patient from receiving any LHRH agonist
12. Pathological complete response following treatment with neoadjuvant therapy
13. History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix or considered a very low risk of recurrence per investigator judgement) unless in complete remission with no therapy for a minimum of 5 years from the date of randomisation
14. Any evidence of severe or uncontrolled systemic diseases which, in the investigator’s opinion precludes participation in the study or compliance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy IBCFS (invasive breast cancer free-survival) as defined by STEEP 2.0 criteria

Secondary endpoints 5

1. Secondary efficacy IDFS(invasive disease-free survival) as defined by STEEP 2.0 criteria DRFS(distant relapse-free survival) as defined by STEEP 2.0 criteria OS(overall survival)
2. Secondary safety Safety endpoints including: • TEAEs(treatment-emergent adverse event), SAEs(serious adverse event) • Clinical laboratory tests and vital signs
3. Secondary COAs(clinical outcome assessment): Proportion of time on study treatment with high side-effect burden as measured by the PGI-TT
4. Secondary COAs (clinical outcome assessment) Change from baseline and TTD(time to deterioration ) of health-related QoL(quality of life) as measured by the 2 global QoL (quality of life) items from the EORTC IL-311 (European Organisation for Research and Treatment of Cancer)
5. Secondary PK(pharmacokinetic(s) Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration)

Investigational products

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

Test 2

Comparator 4

Auxiliary 3

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 Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 8

Locations

16 EU/EEA countries · 248 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 253 files

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

Application history

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