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

• ClinicalTrials.gov Identifier: NCT05774951
• Recruitment Status: Recruiting
• First Posted: March 20, 2023
• Last Update Posted: April 19, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 16, 2023
• First Posted Date: March 20, 2023
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: March 31, 2023
• Estimated Primary Completion Date: April 19, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2023)

Invasive breast cancer-free survival (IBCFS) [ Time Frame: Up to 10 years ]

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.

Original Primary Outcome Measures (submitted: March 7, 2023)

Invasive breast cancer-free survival (IBCFS) [ Time Frame: Up to 10 years ]

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
• Contralateral invasive breast cancer
• Death attributable to any cause.

Current Secondary Outcome Measures (submitted: October 10, 2023)

• Invasive disease-free survival (IDFS) [ Time Frame: Up to 10 years ]
  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) [ Time Frame: Up to 10 years ]
  DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.
• Overall survival (OS) [ Time Frame: Up to 10 years ]
  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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Absolute and percent change from baseline in Clinical Laboratory Parameters [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Absolute and percent change from baseline in Vital Sign Parameters [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Number of participants with abnormal physical examinations [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Pharmacokinetics (PK) [ Time Frame: Until 6 months from treatment start ]
  • Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration)

Original Secondary Outcome Measures (submitted: March 7, 2023)

• Invasive disease-free survival (IDFS) [ Time Frame: Up to 10 years ]
  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
  • Contralateral invasive breast cancer
  • Second primary non-breast invasive cancer
  • Death attributable to any cause.
• Distant relapse-free survival (DRFS) [ Time Frame: Up to 10 years ]
  DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.
• Overall survival (OS) [ Time Frame: Up to 10 years ]
  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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Absolute and percent change from baseline in Clinical Laboratory Parameters [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Absolute and percent change from baseline in Vital Sign Parameters [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Number of participants with abnormal physical examinations [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Change from baseline and time to worsening 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Change from baseline and time to worsening of hot flush as measured by the EORTC-IL-194 item 4. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Change from baseline and time to worsening of vaginal dryness as measured by the EORTC-IL-194 item 15. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• 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) [ Time Frame: Until 28 days after the final dose of study treatment (up to 5 years) ]
• Pharmacokinetics (PK) [ Time Frame: Until 6 months from treatment start ]
  • Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

• Condition: Breast Cancer, Early Breast Cancer

Intervention

• Drug: Camizestrant
  Camizestrant. Experimental. Administered orally
  Other Name: AZD9833
• Drug: Tamoxifen
  Tamoxifen. Comparator. Administered per local approved label
• Drug: Anastrozole
  Anastrozole. Comparator. Administered per local approved label
• Drug: Letrozole
  Letrozole. Comparator. Administered per local approved label
• Drug: Exemestane
  Exemestane. Comparator. Administered per local approved label

Study Arms

• Active Comparator: Arm A: standard endocrine therapy of investigator´s choice
  Continue standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen)
  Interventions:

  • Drug: Tamoxifen
  • Drug: Anastrozole
  • Drug: Letrozole
  • Drug: Exemestane
• Experimental: Arm B: camizestrant
  Camizestrant
  Intervention: Drug: Camizestrant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 7, 2023): 4300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 29, 2036
• Estimated Primary Completion Date: April 19, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Romania, Serbia, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT05774951
• Other Study ID Numbers: D8531C00002; 2022-501024-20-00 ( Other Identifier: EMA - CTIS )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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 Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol
• Supporting Materials: 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 rerefer 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 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. 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

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: April 2024