The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT05774951
Recruitment Status : Recruiting
First Posted : March 20, 2023
Last Update Posted : June 21, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 16, 2023
First Posted Date  ICMJE March 20, 2023
Last Update Posted Date June 21, 2024
Actual Study Start Date  ICMJE March 31, 2023
Estimated Primary Completion Date April 19, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy
Official Title  ICMJE CAMBRIA-1: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Extended Therapy With Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) in Patients With ER+/HER2- Early Breast Cancer and an Intermediate or High Risk of Recurrence Who Have Completed Definitive Locoregional Therapy and at Least 2 Years of Standard Adjuvant Endocrine-Based Therapy Without Disease Recurrence
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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  ICMJE Breast Cancer, Early Breast Cancer
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 7, 2023)
4300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 29, 2036
Estimated Primary Completion Date April 19, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE 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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05774951
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP