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Breast NeoplasmsPhase 2PERIDENONCT03532087

Study to Identify the Impact of Denosumab on the Immune System in Patients With HER2 Negative Breast Cancer

A Phase 2 study testing Denosumab 120 mg and Denosumab 60 mg in people with Breast Neoplasms, run by Borstkanker Onderzoek Groep at 8 sites in Netherlands.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The aim of this prospective, randomized, multicenter, open-label, explorative phase II study is to identify the impact of (neo)adjuvant denosumab on the systemic immunity and local immunologic microenvironment in postmenopausal patients with HER2 negative non-metastatic primary breast cancer. 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 120 mg and Denosumab 60 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
8 sitesNetherlands
Study dates
Feb 2018to Jun 2023
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

  • Postmenopausal, defined as 1 year without menstrual activity, previous bilateral oophorectomy, age older than 60 years or baseline FSH >20 U/l and estradiol <110 pmol/l.
  • Clinical stage T1c + grade 3, stage II or III breast cancer amenable to adjuvant AC-T combination chemotherapy.
  • Measurable disease (breast and/or lymph nodes).
  • Histological proven HER2-negative breast cancer in the core biopsy material.
  • WHO 0-2.
  • Adequate bone marrow function (within 4 weeks prior to randomization): WBC≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l.
Show all 11Show fewer
  • Adequate liver function (within 4 weeks prior to randomization): bilirubin ≤1.5 X upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL.
  • Adequate renal function (within 4 weeks prior to randomization): the calculated creatinine clearance should be ≥50 ml/min.
  • Albumin-adjusted serum calcium > 2.0 mmol/L (8.0mg/dL)
  • Accessible for treatment and follow-up.
  • Written informed consent.

Who cannot join

  • Evidence of distant metastases (M1).
  • History of breast cancer.
  • Prior chemotherapy or radiation therapy.
  • Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
  • Prior or current bisphosphonate or denosumab usage.
  • Serious other diseases as recent (last 6 months) myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias.
Show all 9Show fewer
  • Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), non-healed dental or oral surgery, a current or prior diagnosis of osteonecrosis of the jaw or planned invasive dental procedures for the course of the study.
  • Known hypersensitivity reaction to any of the components of the treatment.
  • Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Netherlands8 sites

  • Ziekenhuisgroep Twente (Twenteborg ZH Almelo)

    Almelo

  • Gelre ziekenhuizen

    Apeldoorn

  • Zuyderland Medisch Centrum (Heerlen)

    Heerlen

  • Spaarne Gasthuis (Hoofddorp)

    Hoofddorp

  • Leiden University Medical Center

    Leiden

  • Fransiscus (Vlietland)

    Schiedam

  • VieCuri Medisch Centrum (Venlo)

    Venlo

  • 't Lange Land Ziekenhuis

    Zoetermeer

Other trials in Netherlands

About this study

Official title: Explorative Trial to Identify the Impact of Denosumab on the Systemic Immunity and Local Immunologic Microenvironment in Postmenopausal Patients With HER2 Negative Breast Cancer

The aim of this prospective, randomized, multicenter, open-label, explorative phase II study is to identify the impact of (neo)adjuvant denosumab on the systemic immunity and local immunologic microenvironment in postmenopausal patients with HER2 negative non-metastatic primary breast cancer.

Read the detailed description

In this study, postmenopausal patients with stage T1c + grade 3, stage II or III, HER2-negative breast cancer, which are planned to undergo surgery followed by adjuvant AC-T chemotherapy, are randomized between no denosumab, denosumab low dosing and denosumab high dosing. Denosumab administration will start one week before surgery and continue until the last chemotherapy cycle.

Being tested
Denosumab 120 mg, Denosumab 60 mg
Keywords
Breast cancer, Denosumab, Chemotherapy, Immunity, Immune system, PERIDENO
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Denosumab 120 mgDrug

    Also called Xgeva

    Denosumab 120 mg every 3 weeks.

  • Denosumab 60 mgDrug

    Also called Prolia

    Denosumab 60 mg every 6 months.

Study groups in NCT03532087
Study groupRoleWhat they receive
No denosumabNo interventionAll patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are not additionally treated with denosumab.
Denosumab 120 mgExperimentalAll patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are additionally treated with denosumab 120 mg every 3 weeks. First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.
Receives: Drug: Denosumab 120 mg
Denosumab 60 mgExperimentalAll patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are additionally treated with denosumab 60 mg every 6 months. First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.
Receives: Drug: Denosumab 60 mg

What is being measured

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

  1. Change in intratumoral T-cell (CD4, CD8 and Treg) numbers and function between the baseline biopsy and the surgical specimen.

    The change will be determined by use of IHC and immunofluorescent stainings.

    Measured: The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.

  2. Change in myeloid cell (M1/M2 Macrophage, MDSC, DC) numbers and function between the baseline biopsy and the surgical specimen.

    The change will be determined by use of IHC and immunofluorescent stainings.

    Measured: The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.

Secondary outcomes (13)

  1. Shift in activated T effector cell levels.

    Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  2. Shift in regulatory T-cell levels.

    Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  3. Change in functional response of T-cells.

    Changes will be determined by comparing PBMCs (using stimulation tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  4. Change in mature and immature myeloid cells (M1/M2 macrophage, MDSC, DC).

    Shifts will be determined by comparing PBMCs (using flow cytometry) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  5. Shift in myeloid cell function.

    Shifts will be determined by comparing PBMCs (using triggering tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  6. Change in stimulation capacity APCs.

    Changes will be determined by comparing PBMCs (using restimulation tests) before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration.

    Measured: Measurements will be done in PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  7. Change in serum levels of RANKL and OPG.

    Changes will be determined by comparing serum before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration, using ELISA.

    Measured: Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  8. Change in serum cytokine levels (TNF-alpha, interleukines, IFN gamma).

    Changes will be determined by comparing serum before start treatment, at day of surgery before surgery and 7 days after last chemotherapy administration, using luminex.

    Measured: Measurements will be done in serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment.

  9. Correlation of tumor measurements with serum measurements.

    Measurements in tumor and serum will be correlated.

    Measured: Measurements will be done in tumor material and serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.

  10. Correlation of tumor measurements with PBMCs measurements.

    Measurements in tumor and PBMCs will be correlated.

    Measured: Measurements will be done in tumor material and PBMCs from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.

  11. Correlation of serum measurements and PBMCs measurements.

    Measurements in serum and PBMCs will be correlated.

    Measured: Measurements will be done in PBMCs/serum from before start treatment, day of surgery and 7 days after last chemotherapy administration, which will be around 8 months after enrolment and tumor material from baseline and surgery.

  12. Toxicity according to NCI CTCAE v4.03.

    Toxicities are graded according to NCI CTCAE v4.03.

    Measured: Toxicity will be assessed from start treatment up to 30 days following the last dose of treatment.

  13. Difference in descriptive event free survival (EFS) at 3 years based on immune response.

    After 3 years of follow up, differences in EFS based on immune response will be determined.

    Measured: EFS will be determined after 3 years.

Timeline

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

  1. First posted22 May 2018
  2. Study startFeb 2018 (estimated)
  3. Primary completionFeb 2021 (estimated)
  4. Study completionJun 2023 (estimated)

Why it stopped: Due to new insights

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
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03532087
Sponsor's protocol ID
BOOG-2017-02
Other IDs
2016-005210-22, 2016
Acronym
PERIDENO
Status last verified
Jul 2019
First submitted
5 Feb 2018
Last updated
18 Jan 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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 Phase 2 study testing Denosumab 120 mg and Denosumab 60 mg in people with Breast Neoplasms, run by Borstkanker Onderzoek Groep at 8 sites in Netherlands.

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 11 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: withdrawn, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Netherlands. 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 withdrawn before enrolling participants, so there are no results.

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?

Change in intratumoral T-cell (CD4, CD8 and Treg) numbers and function between the baseline biopsy and the surgical specimen. (time frame: The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment.). The study lists 2 primary outcomes in all. 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 NCT03532087, 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 18 Jan 2020.

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