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Breast NeoplasmsPhase 2D-BeyondNCT01864798

A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer

A Phase 2 study testing Denosumab in people with Breast Neoplasms, run by Jules Bordet Institute at 6 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
Denosumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
6 sitesin 2 countries
Study dates
Jul 2013to Jan 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female gender
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • 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
  • Non-metastatic operable newly diagnosed primary invasive carcinoma of the breast that is:
  • Histologically confirmed
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  • Primary tumor size greater than 1.5 cm, measured by any of clinical examination, mammography, ultrasound or magnetic resonance imaging
  • Any clinical nodal status
  • Fully operable and not fixed to chest wall.
  • Known HER2 status
  • Known estrogen receptor (ER) status and progesterone receptor status (PgR)
  • 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 %
  • Albumin-adjusted serum calcium ≥ 8.0 mg/dL (≥ 2.0 mmol/L)
  • 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
  • Patients must accept to take calcium and vitamin D supplementation until the completion of the study treatment
  • Signed informed consent form (ICF) for all study procedures according to local regulatory requirements prior to beginning of the study
  • 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.

Who cannot join

  • History of any prior (ipsi and/or contralateral) breast cancer
  • Any "clinical" T4 tumor defined by TNM including inflammatory breast cancer
  • 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)
  • Prior or planned systemic anti-cancer therapy before definitive surgery
  • Unhealed or planned dental/oral surgery, current or previous osteonecrosis or osteomyelitis of the jaw
  • 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
Show all 9Show fewer
  • Active Hepatitis-B virus (HBV), Hepatitis-C virus (HCV) or human immunodeficiency virus (HIV) infection
  • Known hypersensitivity to denosumab
  • Bilateral invasive tumors

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Belgium5 sites

  • Institute Jules Bordet

    Brussels, 1000

  • Hopital Erasme

    Brussels, 1070

  • UZ Leuven

    Leuven, 3000

  • CHU Ambroise Paré

    Mons, 7000

  • CMSE

    Namur, 5000

Other trials in Belgium

Australia1 site

  • Royal Melbourne Hospital

    Victoria, 3050

Other trials in Australia

About this study

Official 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

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.

Read more

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
Being tested
Denosumab
Keywords
Young, Breast Neoplasms, Denosumab, RANKL
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Also called XGEVA

Study groups in NCT01864798
Study groupRoleWhat they receive
DenosumabExperimentalNot described
Receives: Drug: Denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Geometric mean change in tumor Ki67 expression

    Assessed by immunohistochemistry (IHC) from

    Measured: Baseline and surgery at Day 10

Secondary outcomes (10)

  1. Absolute Ki67 responders

    KI 67 responders will be defined as below 2.7% Ki67 IHC staining in the post treatment tumor biopsy

    Measured: Baseline and surgery at Day 10

  2. C-terminal telopeptide (CTX) serum levels

    Measured: Baseline and surgery at Day 10

  3. RANK/RANKL gene expression and signalling

    Assessed by immunohistochemistry (IHC) and RNA sequencing profile in the tumor

    Measured: Baseline and surgery at Day 10

  4. gene expression (AURKA, Ki-67,GGI)

    Change in tumor proliferation rates using gene expression (single genes and gene modules, i.e. AURKA, Ki-67) and proliferation-related gene modules, i.e. GGI) in the tumor from baseline to prior to surgery

    Measured: Baseline and surgery at Day 10

  5. TUNEL and caspase-3 apoptosis markers

    Change in tumor apoptosis rates as measured using TUNEL and caspase-3 IHC from baseline to prior to surgery

    Measured: Baseline and surgery at Day 10

  6. expression of immature mammary epithelial cell population: MaSCs, luminal progenitors , ALDH1

    Change in expression levels from genes corresponding to immature mammary epithelial cell populations (MaSCs and luminal progenitors developed by Lim et al; Nature 2009), and in IHC expression of ALDH1, a stem cell marker in the tumor

    Measured: Baseline and surgery at Day 10

  7. gene expression of the estrogen pathways (i.e. ESR1, PgR, BCL2) and estrogen-related gene expression modules (i.e. ESR module)

    Change in expression levels from single genes related to the estrogen pathways (i.e. ESR1, PgR, BCL2 using both gene expression and IHC) and estrogen-related gene expression modules (i.e. ESR module) in the tumor

    Measured: Baseline and surgery at Day 10

  8. immune related genes

    Change in expression levels from single genes related to immune pathways using both gene expression and IHC, and in immune-related gene expression modules, to explore the hypothesis that RANKL can modulate T regulatory cells in the tumor

    Measured: Baseline and surgery at Day 10

  9. Quantity of tumor infiltrating lymphocytes

    Change in the quantity of tumor infiltrating lymphocytes as measured by percentage infiltration of surrounding tumor stroma and intra-tumoral on the H\&E slide pre and post treatment

    Measured: Baseline and surgery at Day 10

  10. Safety and tolerability of a short course of denosumab

    Measured: Day 1, day 8 and surgery Day 10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2013 (estimated)
  2. Study startJul 2013
  3. Primary completionJan 2017
  4. Study completionJan 2017

Why it stopped: Poor recruitment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01864798
Sponsor's protocol ID
IJB-BCTL- 20119167
Other IDs
2011-006224-21
Acronym
D-Beyond
Status last verified
Nov 2018
First submitted
21 May 2013
Last updated
27 Nov 2018
Results posted
No
Data monitoring committee
No

Publications

  • Gomez-Aleza C, Nguyen B, Yoldi G, Ciscar M, Barranco A, Hernandez-Jimenez E, Maetens M, Salgado R, Zafeiroglou M, Pellegrini P, Venet D, Garaud S, Trinidad EM, Benitez S, Vuylsteke P, Polastro L, Wildiers H, Simon P, Lindeman G, Larsimont D, Van den Eynden G, Velghe C, Rothe F, Willard-Gallo K, Michiels S, Munoz P, Walzer T, Planelles L, Penninger J, Azim HA Jr, Loi S, Piccart M, Sotiriou C, Gonzalez-Suarez E. Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells. Nat Commun. 2020 Dec 10;11(1):6335. doi: 10.1038/s41467-020-20138-8.

    PubMed 33303745

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab in people with Breast Neoplasms, run by Jules Bordet Institute at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Belgium, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Geometric mean change in tumor Ki67 expression (time frame: Baseline and surgery at Day 10). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01864798, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2018; AzTrials last refreshed its copy on 1 Nov 2026.

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