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Breast Neoplasm FemaleEarly Phase 1D-BIOMARKNCT03691311

Biomarker Study of the Antitumoral Activity of Denosumab in the Pre- Operative Setting of Early Breast Cancer

A Early Phase 1 study testing Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] in people with Breast Neoplasm Female and Stage I Breast Cancer, run by Institut Català d'Oncologia at 1 site in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a biomarker study designed to test the preclinically generated hypothesis of anti-tumoral activity of denosumab in patients with early breast cancer candidates a tumour excision Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteSpain
Study dates
5 Jul 2018to 5 Feb 2023
Phase
Early Phase 1
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

  • Understand and sign Informed Consent for this study.
  • Women ≥ than 18 years, (the inclusion process will be modified to recruit at least 24 premenopausal patients).
  • Capable, under investigator judgment, to understand the non-therapeutic nature of the study.
  • Diagnosed with invasive breast cancer in early, curable, stage (I or II) candidate to radical surgery as first therapeutic approach.
  • Her2 negative receptor status.
  • Any estrogen, progesterone status (the inclusion process will be modified to recruit at least 24 patients with TNBC tumors).
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  • No previous systemic treatment for any malignancy.
  • No ongoing treatment with denosumab or bisphosphonates.
  • Tumour amenable for baseline Biopsy and punch-Biopsy after excision.
  • Adequate Serum calcium or albumin-adjusted serum calcium ≥ 2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)
  • No prior history or current evidence of osteonecrosis of the jaw
  • No Active dental or jaw condition which requires oral surgery, including tooth extraction. Noplanned invasive dental procedures.
  • General Laboratory test within normality or with non-relevant deviations of normality as per investigator judgment.
  • Patients must have a normal organ and bone marrow function as defined local standards: Leukocytes, Absolute neutrophil count, Platelets, Total bilirubin, AST/ALT/GOT/GPT, Creatinine, Creatinine clearance, Magnesium, Phosphorus.
  • Subject with reproductive potential must be willing to use, in combination with her partner, 2 acceptable methods of effective contraception or practice sexual abstinence throughout the study and continue for 6 months after study duration. Subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures".

Who cannot join

  • Invasive breast cancer non-amenable to surgical excision as first therapeutic approach.
  • HER2-positive Breast Cancer
  • Metastatic breast cancer or other condition that recommends other treatment than surgery as the primary therapeutic approach.
  • Prior systemic treatment for any malignancy.
  • Treatment with denosumab contraindicated.
  • Bleeding diathesis or other concomitant condition that contraindicate inclusion in the study as per investigator judgment.
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  • High risk of ONJ or hypocalcemia:
  • Inadequate Serum calcium or albumin-adjusted serum calcium < 2.0 mmol/L (8.0 mg/dL) or > 2.9 mmol/L (11.5 mg/dL).
  • Prior history or current evidence of osteonecrosis of the jaw
  • Active dental or jaw condition which requires oral surgery, including tooth extraction. Planned invasive dental procedures.
  • 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 is pregnant or breast feeding or planning to become pregnant / breastfeed while on study through 6 months after the end of treatment.
  • Subject is of child bearing potential and is not willing to use, in combination with her partner, two highly effective methods of contraception or abstinence during treatment and for 5 months after the end oftreatment.
  • Patients have prior history or current evidence of osteonecrosis or osteomyelitis of the jaw.
  • Patients have active dental or jaw condition which requires oral surgery, including tooth extraction.
  • Patients have non-healed dental or oral surgery, including tooth extraction.
  • Patients with planned invasive dental procedures for the course of the study.
  • Ongoing treatment with denosumab or bisphosphonates

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Institut Català d'Oncologia - L'Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08908

Other trials in Spain

About this study

Official title: An Open Label Biomarker Pilot Study of the Antitumoral Activity of Denosumab in the Pre- Operative Setting of Early Breast Cancer

This is a biomarker study designed to test the preclinically generated hypothesis of anti-tumoral activity of denosumab in patients with early breast cancer candidates a tumour excision

Read the detailed description

This is a biomarker study designed to test in patients the preclinically generated hypothesis of anti-tumoral activity of denosumab.The main objective is to demonstrate the antiproliferative and/or pro-apoptotic activity of denosumab in early breast cancer. Other endpoints are to correlate denosumab activity with RANK and RANKL expressions through mRNA and protein; to characterize the differential antiproliferative activity of denosumab between different phenotypes of breast cancer; to identify biomarkers, to identify global changes in gene expression and validate the activity of RANKL antibody in clinical samples. A total of 60 patients with early breast cancer (Stages I and II) candidates to tumor excision as first therapeutic approach will be randomized 2:1, a treatment arm that will receive two doses of denosumab following diagnosis, and a control arm that will not receive treatment. At least 24 patients with hormone receptor negative breast cancer and 24 premenopausal patients will be included in the study.

Being tested
Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Keywords
rank, rankl, denosumab
Medical subject headings
Breast Neoplasms, Osteopetrosis, Autosomal Recessive 7, Osteopetrosis, mild autosomal recessive form

What participants receive

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

  • Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]Drug

    Two injections on days 1 and 8 previous to surgery breast cancer excision

Study groups in NCT03691311
Study groupRoleWhat they receive
DenosumabExperimentalDenosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Receives: Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
ControlNo interventionControl group

What is being measured

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

  1. Antiproliferative and/or pro-apoptotic activity of denosumab

    Changes in the percentage of tumor cells expressing Ki67 and/or cleaved caspase 3 between Biopsy A and Biopsy B.

    Measured: From first biopsy until surgery intervention, which is around four weeks after enrolment

Secondary outcomes (4)

  1. Correlation between antiproliferative activity of denosumab and Rank/RankL expression

    Modified ratio of Rank/RankL: MR={log(RANK) -1.2} / log(RANKL) as described in Palafox et al [10].

    Measured: From first biopsy until surgery intervention, which is around four weeks after enrolment

  2. Differential antiproliferative activity of denosumab among the different phenotypes of breast cancers.

    Ki67 estimations for each phenotype

    Measured: From first biopsy until surgery intervention, which is around four weeks after enrolment

  3. Differential antiproliferative activity of denosumab among pre and post menopausal patients

    Ki67 estimations for each menopausal group

    Measured: From first biopsy until surgery intervention, which is around four weeks after enrolment

  4. Safety of denosumab and biopsy procedures in terms of Frequency of adverse events (CTCAE V4.)

    Frequency of adverse events derived from denosumab treatment and biopsy procedures

    Measured: From first biopsy until surgery intervention, which is around four weeks after enrolment

Timeline

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

  1. First posted1 Oct 2018
  2. Study start5 Jul 2018
  3. Primary completion5 Jul 2022 (estimated)
  4. Study completion5 Feb 2023 (estimated)

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
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a parallel two arms trial randomized in 2:1 proportions to intervention group vs control group. . At least 24 patients with hormone receptor negative breast cancer and 24 premenopausal patients will be included in the study so allocation of patients without any of these two characteristics will be restricted depending on the overall characteristics of the included population
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03691311
Sponsor's protocol ID
ICO 13-001
Other IDs
2016-002678-11, 20119112, 2016
Acronym
D-BIOMARK
Status last verified
Nov 2021
First submitted
4 Sep 2018
Last updated
3 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

    PubMed 38979716

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] in people with Breast Neoplasm Female and Stage I Breast Cancer, run by Institut Català d'Oncologia at 1 site in Spain.

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 15 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

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?

Antiproliferative and/or pro-apoptotic activity of denosumab (time frame: From first biopsy until surgery intervention, which is around four weeks after enrolment). 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 NCT03691311, 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 3 Nov 2021.

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