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
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.
Arms & interventions
- DrugCamizestrant
Camizestrant. Experimental. Administered orally
- DrugTamoxifen
Tamoxifen. Comparator. Administered per local approved label
- DrugAnastrozole
Anastrozole. Comparator. Administered per local approved label
- DrugLetrozole
Letrozole. Comparator. Administered per local approved label
- DrugExemestane
Exemestane. Comparator. Administered per local approved label
Outcome measures
Primary
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.
Time frame: Up to 10 years
Secondary
Invasive disease-free survival (IDFS)
Time frame: Up to 10 years
Distant relapse-free survival (DRFS)
Time frame: Up to 10 years
Overall survival (OS)
Time frame: Up to 10 years
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)
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
Eligibility criteria
Study locations (127)
Research Site
Birmingham, Alabama, 35205
Research Site
Dothan, Alabama, 36303
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Anchorage, Alaska, 99508
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Chandler, Arizona, 85224
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Hot Springs, Arkansas, 71913
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Anaheim, California, 92801
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Beverly Hills, California, 90211
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Concord, California, 94520
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Corona, California, 92882
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Fountain Valley, California, 92708
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Greenbrae, California, 94904
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Los Alamitos, California, 90720
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Palo Alto, California, 94304
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San Diego, California, 92121
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San Diego, California, 92123
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Whittier, California, 90603
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Aurora, Colorado, 80045
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Hartford, Connecticut, 06102
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Fort Myers, Florida, 33901
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Gainesville, Florida, 32603
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Miami Beach, Florida, 33140
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Orlando, Florida, 32806
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Plantation, Florida, 33324
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Port Saint Lucie, Florida, 34952
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Saint Augustine, Florida, 32086
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St. Petersburg, Florida, 33705
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St. Petersburg, Florida, 33709
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Tallahassee, Florida, 32308
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West Palm Beach, Florida, 33401
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Winter Haven, Florida, 33880
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Atlanta, Georgia, 30310
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Atlanta, Georgia, 30318
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Columbus, Georgia, 31904
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Honolulu, Hawaii, 96813
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Chicago, Illinois, 60608
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Chicago, Illinois, 60637
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Decatur, Illinois, 62526
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Elmhurst, Illinois, 60126
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Hinsdale, Illinois, 60521
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Park Ridge, Illinois, 60068
Research Site
Park Ridge, Illinois, 60068
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Fort Wayne, Indiana, 46804
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Iowa City, Iowa, 52242
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Fort Mitchell, Kentucky, 41017
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Lexington, Kentucky, 40536
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Louisville, Kentucky, 40202
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Baton Rouge, Louisiana, 70809
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Brewer, Maine, 04412
Research Site
Scarborough, Maine, 04074
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Frederick, Maryland, 21702
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Glenn Dale, Maryland, 20769
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Silver Spring, Maryland, 20910
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Towson, Maryland, 21204
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Boston, Massachusetts, 02111
Research Site
Hyannis, Massachusetts, 02601
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Ann Arbor, Michigan, 48109
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Detroit, Michigan, 48202
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East Lansing, Michigan, 48824
Research Site
Lansing, Michigan, 48910
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Royal Oak, Michigan, 48073
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Independence, Missouri, 64057
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Lincoln, Nebraska, 68506
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Las Vegas, Nevada, 89148
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Laconia, New Hampshire, 03246
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Belleville, New Jersey, 07109
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Farmington, New Mexico, 87401
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Santa Fe, New Mexico, 87505
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East Syracuse, New York, 13057
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New Hyde Park, New York, 11042
Research Site
New York, New York, 10011
Research Site
New York, New York, 10019
Research Site
New York, New York, 10029
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Stony Brook, New York, 11794
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The Bronx, New York, 10461
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White Plains, New York, 10601
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Charlotte, North Carolina, 28204
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Durham, North Carolina, 27710-0001
Research Site
Greensboro, North Carolina, 27403
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Raleigh, North Carolina, 27607
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Rocky Mount, North Carolina, 27804
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Winston-Salem, North Carolina, 27103
Research Site
Winston-Salem, North Carolina, 27104
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Cincinnati, Ohio, 45219
Research Site
Cincinnati, Ohio, 45255
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Cleveland, Ohio, 44106
Research Site
Cleveland, Ohio, 44195
Research Site
Youngstown, Ohio, 44504
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Clairton, Pennsylvania, 15025
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Philadelphia, Pennsylvania, 19106
Research Site
Philadelphia, Pennsylvania, 19111
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Pittsburgh, Pennsylvania, 15213
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Reading, Pennsylvania, 19611
Research Site
State College, Pennsylvania, 16803
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Providence, Rhode Island, 02903
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Lancaster, South Carolina, 29720
Research Site
Spartanburg, South Carolina, 29303
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Aberdeen, South Dakota, 57401
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Mitchell, South Dakota, 57301
Research Site
Pierre, South Dakota, 57501
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Sioux Falls, South Dakota, 57105
Research Site
Yankton, South Dakota, 57078
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Chattanooga, Tennessee, 37404
Research Site
Knoxville, Tennessee, 37920
Research Site
Nashville, Tennessee, 37203
Research Site
Nashville, Tennessee, 37204
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Austin, Texas, 78731
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Dallas, Texas, 75230
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Denton, Texas, 76201
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Houston, Texas, 77024
Research Site
Houston, Texas, 77030
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Irving, Texas, 75063
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Ogden, Utah, 84405
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Salt Lake City, Utah, 84106
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Fairfax, Virginia, 22031
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Lynchburg, Virginia, 24501
Research Site
Midlothian, Virginia, 23114
Research Site
Reston, Virginia, 20190
Research Site
Richmond, Virginia, 23235
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Seattle, Washington, 98101
Research Site
Seattle, Washington, 98104
Research Site
Spokane, Washington, 99202
Research Site
Tacoma, Washington, 98405
Research Site
Charleston, West Virginia, 25304
Research Site
Morgantown, West Virginia, 26505
Research Site
Appleton, Wisconsin, 54911
Research Site
Madison, Wisconsin, 53792
Research Site
Milwaukee, Wisconsin, 53226
References
- Hamilton EP, Loibl S, Bachelot T, Gnant M, Niikura N, Park YH, Tolaney SM, Pistilli B, Rastogi P, Saini KS, Gioni I, Johnston S, Nunes R, Quintana A, Stuart M, Syta E, Walding A, Klinowska T, Mayer IA. CAMBRIA-1 & CAMBRIA-2 phase III trials: camizestrant versus standard endocrine therapy in ER+/HER2- early breast cancer. Future Oncol. 2025 Mar;21(7):795-806. doi: 10.1080/14796694.2025.2459548. Epub 2025 Feb 27.(PubMed)