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A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy (CAMBRIA-1)

Primary Purpose

Breast Cancer, Early Breast Cancer

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Camizestrant

Tamoxifen

Anastrozole

Letrozole

Exemestane

About this trial

This is an interventional treatment trial for Breast Cancer, Early Breast Cancer focused on measuring ER+, HER2-, breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Women and Men, ≥18 years at the time of screening (or per national guidelines) Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with high or intermediate risk of recurrence, based on clinical-pathological risk features, as defined in the protocol. Completed adequate (definitive) locoregional therapy (surgery with or without radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant chemotherapy Completed at least 2 years but no more than 5 years (+3 months) of adjuvant ET (+/- CDK4/6 inhibitor) Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Adequate organ and marrow function Exclusion criteria: Inoperable locally advanced or metastatic breast cancer Pathological complete response following treatment with neoadjuvant therapy History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix or considered at 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 Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion precludes participation in the study or compliance Known LVEF <50% with heart failure NYHA Grade ≥2. Mean resting QTcF interval >480 ms at screening Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions Any concurrent anti-cancer treatment not specified in the protocol with the exception of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors (eg, denosumab) Previous treatment with camizestrant, investigational SERDs/investigational ER targeting agents, or fulvestrant Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: standard endocrine therapy of investigator´s choice

Arm B: camizestrant

Arm Description

Continue standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen)

Camizestrant

Outcomes

Primary Outcome Measures

Invasive breast cancer-free survival (IBCFS)

IBCFS is defined as time from randomisation until date of first occurrence of: Invasive ipsilateral breast tumour recurrence (invasive IBTR) Locoregional invasive breast cancer recurrence Distant recurrence Invasive contralateral breast cancer Death attributable to any cause.

Secondary Outcome Measures

Invasive disease-free survival (IDFS)

IDFS is defined as time from randomisation until date of first occurrence of one of the following events: Invasive ipsilateral breast tumor recurrence (invasive IBTR) Locoregional invasive breast cancer recurrence Distant recurrence Invasive contralateral breast cancer Second primary non-breast invasive cancer Death attributable to any cause.

Distant relapse-free survival (DRFS)

DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.

Overall survival (OS)

OS is defined as time from randomisation until death from any cause.

Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)

Absolute and percent change from baseline in Clinical Laboratory Parameters

Absolute and percent change from baseline in Vital Sign Parameters

Number of participants with abnormal physical examinations

Change from baseline of arthralgia as measured by the EORTC-IL-194 (European Organisation for Research and Treatment of Cancer) item 10. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Change from baseline of hot flush as measured by the EORTC-IL-194 item 4. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Change from baseline of vaginal dryness as measured by the EORTC-IL-194 item 15. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Proportion of patients experiencing each level of symptomatic AEs of arthralgia as measured by the EORTC-IL-194 item 10. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Proportion of patients experiencing each level of symptomatic AEs of hot flush as measured by the EORTC-IL-194 item 4. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Proportion of patients experiencing each level of symptomatic AEs of vaginal dryness as measured by the EORTC-IL-194 item 15. EORTC-IL-194 uses 0 - 4 scale (higher score is worse)

Change from baseline and TTD (time to deterioration ) of health-related QoL (quality of life) as measured by the 2 global QoL items from the EORTC-QLQ-C30 items 11 and 12. EORTC-QLQ-C30 uses 0 - 4 scale (higher score is worse)

Pharmacokinetics (PK)

• Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration)

Full Information

NCT ID

NCT05774951

First Posted

February 16, 2023

Last Updated

October 10, 2023

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT05774951

Brief Title

A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy

Acronym

CAMBRIA-1

Official Title

A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Extended Therapy With Camizestrant Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) in Patients With ER+/HER2- Early Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 31, 2023 (Actual)

Primary Completion Date

April 19, 2027 (Anticipated)

Study Completion Date

May 29, 2036 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer with intermediate or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months.

Detailed Description

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months. The eligible patients must have intermediate or high risk of recurrence, as defined by specified clinical and biologic criteria. Prior use of CDK4/6 inhibitors is permitted. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Early Breast Cancer

Keywords

ER+, HER2-, breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Patients will be randomised in a 1:1 ratio to one of the following arms: Arm A: Continue standard ET of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) Arm B: Camizestrant

Masking

None (Open Label)

Allocation

Randomized

Enrollment

4300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A: standard endocrine therapy of investigator´s choice

Arm Type

Active Comparator

Arm Description

Continue standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen)

Arm Title

Arm B: camizestrant

Arm Type

Experimental

Arm Description

Camizestrant

Intervention Type

Drug

Intervention Name(s)

Camizestrant

Other Intervention Name(s)

AZD9833

Intervention Description

Camizestrant. Experimental. Administered orally

Intervention Type

Drug

Intervention Name(s)

Tamoxifen

Intervention Description

Tamoxifen. Comparator. Administered per local approved label

Intervention Type

Drug

Intervention Name(s)

Anastrozole

Intervention Description

Anastrozole. Comparator. Administered per local approved label

Intervention Type

Drug

Intervention Name(s)

Letrozole

Intervention Description

Letrozole. Comparator. Administered per local approved label

Intervention Type

Drug

Intervention Name(s)

Exemestane

Intervention Description

Exemestane. Comparator. Administered per local approved label

Primary Outcome Measure Information:

Title

Invasive breast cancer-free survival (IBCFS)

Description

Time Frame

Up to 10 years

Secondary Outcome Measure Information:

Title

Invasive disease-free survival (IDFS)

Description

Time Frame

Up to 10 years

Title

Distant relapse-free survival (DRFS)

Description

DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.

Time Frame

Up to 10 years

Title

Overall survival (OS)

Description

OS is defined as time from randomisation until death from any cause.

Time Frame

Up to 10 years

Title

Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)

Time Frame