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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01077154




Registration number
NCT01077154
Ethics application status
Date submitted
4/02/2010
Date registered
26/02/2010
Date last updated
28/09/2021

Titles & IDs
Public title
Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE)
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab as Adjuvant Treatment for Women With Early-Stage Breast Cancer at High Risk of Recurrence (D-CARE)
Secondary ID [1] 0 0
2009-011299-32
Secondary ID [2] 0 0
20060359
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Denosumab

Placebo comparator: Placebo - Participants received placebo subcutaneous injections once every 4 weeks for 6 months followed by placebo subcutaneous injections once every 3 months for 4.5 years.

Experimental: Denosumab - Participants received denosumab 120 mg subcutaneous injections once every 4 weeks for 6 months followed by denosumab 120 mg subcutaneous injections once every 3 months for 4.5 years.


Treatment: Drugs: Placebo
Administered subcutaneously for up to 5 years

Treatment: Drugs: Denosumab
Administered subcutaneously for up to 5 years

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Bone Metastasis-free Survival (BMFS)
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary outcome [1] 0 0
Disease-free Survival (DFS)
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary outcome [2] 0 0
Disease-free Survival (DFS) in the Postmenopausal Subset
Timepoint [2] 0 0
From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
From randomization until the end of study; median (minimum, maximum) time on study was 72.7 (0, 92) and 72.3 (0, 92) months in each treatment group respectively.
Secondary outcome [4] 0 0
Distant Recurrence-free Survival
Timepoint [4] 0 0
From randomization until the primary analysis data cut-off date of 31 August 2017; median (minimum, maximum) time on study was 67.2 (0.0, 85.9) and 67.0 (0.0, 86.6) months in each treatment group respectively.

Eligibility
Key inclusion criteria
* Histologically confirmed, American Joint Committee on Cancer (AJCC) stage II or III breast cancer
* High risk of breast cancer recurrence, defined as documented evidence of one or more of the following criteria:

i) Biopsy evidence of breast cancer in regional lymph node(s) (LN) (node-positive disease); Nodal micrometastases only are not considered node positive ii) Tumor size > 5 cm (T3) or locally advanced disease (T4)
* Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and HER-2 status
* Subjects must be receiving or be scheduled to receive standard of care systemic adjuvant or neoadjuvant chemotherapy and/or endocrine therapy and/or HER-2 targeted therapy
* For subjects receiving adjuvant therapy only:
* subjects must have undergone complete resection of the primary tumor with clean surgical margins, or subjects must have undergone resection of the primary tumor and be scheduled for further treatment of the primary tumor with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
* Time between definitive surgery and randomization must be = 12 weeks. Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)
* Subjects with node positive disease must have undergone treatment of axillary LN with curative intent, or subjects must be scheduled for further treatment of regional lymph nodes with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
* Subjects must not have received prior neoadjuvant treatment. Endocrine treatment for less than 30 days prior to surgery is not considered prior neoadjuvant treatment
* For subjects receiving neoadjuvant therapy only:
* Time between start of neoadjuvant treatment and randomization must be = 8 weeks and subjects must be scheduled to undergo definitive treatment (including surgery and/or radiotherapy) with curative intent within approximately 9 months of starting neoadjuvant treatment
* Female subjects with age = 18 years
* Subjects with reproductive potential must have a negative pregnancy test within 14 days before randomization
* Serum calcium or albumin-adjusted serum calcium = 2.0 mmol/L (8.0 mg/dL) and = 2.9 mmol/L (11.5 mg/dL)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Written informed consent before any study-specific procedure is performed
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior or current evidence of any metastatic involvement of any distant site
* History of breast cancer (other than ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) prior to the current diagnosis
* Osteoporosis requiring treatment at the time of randomization or treatment considered likely to become necessary within the subsequent six months
* Any prior or synchronous malignancy (other than breast cancer), except i) Malignancy treated with curative intent and with no evidence of disease for = 5 years prior to enrollment and considered to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
* Active infection with Hepatitis B virus or Hepatitis C virus
* Known infection with human immunodeficiency virus (HIV)
* Prior history or current evidence of osteomyelitis/osteonecrosis of the jaw
* Active dental or jaw condition which requires oral surgery
* Planned invasive dental procedure for the course of the study
* Non-healed dental or oral surgery
* Use of oral bisphosphonates within the past 1 year
* Prior or current IV bisphosphonate administration
* Prior administration of denosumab
* Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or investigational drug study(s), or subject is receiving other investigational agent(s)
* Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment.
* Subject is of child bearing potential and is not willing to use, in combination with her partner, 2 highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment
* Subject has known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D)
* Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
* Any major medical or psychiatric disorder that in the opinion of the investigator prevent the subject from completing the study or interfere with the interpretation of the study results

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Caringbah
Recruitment hospital [3] 0 0
Research Site - Kogarah
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Research Site - Tweed Heads
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Research Site - Wahroonga
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Research Site - Bedford Park
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Research Site - Bentleigh East
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Research Site - East Melbourne
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Research Site - Fitzroy
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Research Site - Footscray
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Research Site - Frankston
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Research Site - Heidelberg
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Research Site - Malvern
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Research Site - Parkville
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Research Site - Ringwood East
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Research Site - Warrnambool
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Research Site - Wodonga
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Research Site - Perth
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Research Site - Subiaco
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2229 - Caringbah
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2217 - Kogarah
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2485 - Tweed Heads
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2076 - Wahroonga
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [8] 0 0
3002 - East Melbourne
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy
Recruitment postcode(s) [10] 0 0
3011 - Footscray
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3199 - Frankston
Recruitment postcode(s) [12] 0 0
3084 - Heidelberg
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3144 - Malvern
Recruitment postcode(s) [14] 0 0
3050 - Parkville
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3121 - Richmond
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3135 - Ringwood East
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3280 - Warrnambool
Recruitment postcode(s) [18] 0 0
3690 - Wodonga
Recruitment postcode(s) [19] 0 0
6000 - Perth
Recruitment postcode(s) [20] 0 0
6008 - Subiaco
Recruitment outside Australia
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Massachusetts
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Missouri
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Kanagawa
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Kyoto
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Sheffield
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.