Trial Review

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01864798




Registration number
NCT01864798
Ethics application status
Date submitted
21/05/2013
Date registered
30/05/2013
Date last updated
27/11/2018

Titles & IDs
Public title
A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer
Scientific title
A Pre-Operative Window Study Evaluating Denosumab, a RANKligand (RANKL) Inhibitor and Its Biological Effects in Young Premenopausal Women Diagnosed With Early Breast Cancer
Secondary ID [1] 0 0
2011-006224-21
Secondary ID [2] 0 0
IJB-BCTL- 20119167
Universal Trial Number (UTN)
Trial acronym
D-Beyond
Linked study record

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

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

Experimental: Denosumab -


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

Outcomes
Primary outcome [1] 0 0
Geometric mean change in tumor Ki67 expression
Timepoint [1] 0 0
Baseline and surgery at Day 10
Secondary outcome [1] 0 0
Absolute Ki67 responders
Timepoint [1] 0 0
Baseline and surgery at Day 10
Secondary outcome [2] 0 0
C-terminal telopeptide (CTX) serum levels
Timepoint [2] 0 0
Baseline and surgery at Day 10
Secondary outcome [3] 0 0
RANK/RANKL gene expression and signalling
Timepoint [3] 0 0
Baseline and surgery at Day 10
Secondary outcome [4] 0 0
gene expression (AURKA, Ki-67,GGI)
Timepoint [4] 0 0
Baseline and surgery at Day 10
Secondary outcome [5] 0 0
TUNEL and caspase-3 apoptosis markers
Timepoint [5] 0 0
Baseline and surgery at Day 10
Secondary outcome [6] 0 0
expression of immature mammary epithelial cell population: MaSCs, luminal progenitors , ALDH1
Timepoint [6] 0 0
Baseline and surgery at Day 10
Secondary outcome [7] 0 0
gene expression of the estrogen pathways (i.e. ESR1, PgR, BCL2) and estrogen-related gene expression modules (i.e. ESR module)
Timepoint [7] 0 0
Baseline and surgery at Day 10
Secondary outcome [8] 0 0
immune related genes
Timepoint [8] 0 0
Baseline and surgery at Day 10
Secondary outcome [9] 0 0
Quantity of tumor infiltrating lymphocytes
Timepoint [9] 0 0
Baseline and surgery at Day 10
Secondary outcome [10] 0 0
Safety and tolerability of a short course of denosumab
Timepoint [10] 0 0
Day 1, day 8 and surgery Day 10

Eligibility
Key inclusion criteria
1. Female gender

2. Age = 18 years

3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

4. Premenopausal status defined as the presence of active menstrual cycle or normal
menses during the 6 weeks preceding the start of study treatment. Biochemical evidence
of phase of menstrual cycle is required (estradiol, FSH and LH). In women previously
exposed to hysterectomy,or were using hormonal intrauterine device at the time of
enrolment, premenopausal levels of estradiol, FSH and LH are required to be eligible

5. Non-metastatic operable newly diagnosed primary invasive carcinoma of the breast that
is:

1. Histologically confirmed

2. Primary tumor size greater than 1.5 cm, measured by any of clinical examination,
mammography, ultrasound or magnetic resonance imaging

3. Any clinical nodal status

4. Fully operable and not fixed to chest wall.

6. Known HER2 status

7. Known estrogen receptor (ER) status and progesterone receptor status (PgR)

8. Patient has adequate bone marrow and organ function as shown by:

- Absolute neutrophil count (ANC) = 1.5 x 109/L

- Platelets = 100 x 109/L

- Hemoglobin (Hgb) = 9.0 g/dL

- Serum creatinine = 1.5 x ULN

- Total serum bilirubin = 1.5 x ULN (in patients with known Gilbert Syndrome, a
total bilirubin = 3.0 x ULN, with direct bilirubin = 1.5 x ULN)

- AST and ALT = 1.5 x ULN

- Random blood sugar (RBS) = 200 mg/dL or = 11.1 mmol/L

- Glycosylated hemoglobin (HbA1c) = 8 %

9. Albumin-adjusted serum calcium = 8.0 mg/dL (= 2.0 mmol/L)

10. Women of childbearing potential must agree to use an active local contraception method
for the duration of the study and for at least 7 months after the last dose of study
treatment

11. Patients must accept to take calcium and vitamin D supplementation until the
completion of the study treatment

12. Signed informed consent form (ICF) for all study procedures according to local
regulatory requirements prior to beginning of the study

13. Patients must accept to make available tumor and normal tissue samples for submission
to central laboratory at the Jules Bordet Institute, Brussels, Belgium, to conduct
translational studies as part of this protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of any prior (ipsi and/or contralateral) breast cancer

2. Any "clinical" T4 tumor defined by TNM including inflammatory breast cancer

3. History of non-breast malignancies within the 5 years prior to study entry (except
carcinoma in situ of the cervix, of the colon, melanoma in situ and basal cell and
squamous cell carcinomas of the skin)

4. Prior or planned systemic anti-cancer therapy before definitive surgery

5. Unhealed or planned dental/oral surgery, current or previous osteonecrosis or
osteomyelitis of the jaw

6. Pregnant or lactating women or women of childbearing potential without a negative
serum or urinary pregnancy test within 7 days prior to starting study treatment;
irrespective of the method of contraception used

7. Active Hepatitis-B virus (HBV), Hepatitis-C virus (HCV) or human immunodeficiency
virus (HIV) infection

8. Known hypersensitivity to denosumab

9. Bilateral invasive tumors

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2017
Sample size
Target
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Victoria
Recruitment postcode(s) [1] 0 0
3050 - Victoria
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Belgium
State/province [3] 0 0
Mons
Country [4] 0 0
Belgium
State/province [4] 0 0
Namur

Funding & Sponsors
Primary sponsor type
Other
Name
Jules Bordet Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Melbourne Health
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a prospective, single arm phase IIa trial in which patients with early breast cancer
will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart
(maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be
collected at baseline and at surgery. Post-operative treatment will be at the discretion of
the investigator.

Primary objective: to determine if a short course of RANKL inhibition with denosumab can
induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry
(IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

Secondary objectives:

- To determine the number of absolute Ki67 responders after a short course of denosumab
(defined as <2.7% IHC staining in the post treatment tumor biopsy).

- To determine the effects of a short course of denosumab on serum C-terminal telopeptide
levels (CTX).

- To determine the effects of a short course of denosumab on RANK/RANKL gene expression
and signaling as assessed by immunohistochemistry (IHC) and RNA sequencing in the tumor.

- To determine the effect of a short course of denosumab on tumor apoptosis rates using
IHC

- To determine the effect of a short course of denosumab on modulating the immature
mammary epithelial cell populations in the tumor.

- To determine the effect of a short course of denosumab on estrogen signaling pathways in
the tumor.

- To determine the effect of a short course of denosumab on various immune

- To determine effect of safety profile of denosumab
Trial website
https://clinicaltrials.gov/ct2/show/NCT01864798
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martine J Piccart, Prof.
Address 0 0
Jules Bordet Institute
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01864798