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

NCT ID: NCT03532087

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2023-06-30

Brief 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.

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.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

No denosumab

All patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are not additionally treated with denosumab.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Denosumab 120 mg

All 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.

Group Type: EXPERIMENTAL

Denosumab 120 mg

Intervention Type: DRUG

Denosumab 120 mg every 3 weeks.

Denosumab 60 mg

All 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.

Group Type: EXPERIMENTAL

Denosumab 60 mg

Intervention Type: DRUG

Denosumab 60 mg every 6 months.

Interventions

Denosumab 120 mg

Denosumab 120 mg every 3 weeks.

Intervention Type: DRUG

Denosumab 60 mg

Denosumab 60 mg every 6 months.

Intervention Type: DRUG

Other Intervention Names

Xgeva; Prolia

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith R Kroep, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Gerrit-Jan Liefers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Sjoerd H van der Burg, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Ziekenhuisgroep Twente (Twenteborg ZH Almelo)

Almelo, , Netherlands

Gelre ziekenhuizen

Apeldoorn, , Netherlands

Zuyderland Medisch Centrum (Heerlen)

Heerlen, , Netherlands

Spaarne Gasthuis (Hoofddorp)

Hoofddorp, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Fransiscus (Vlietland)

Schiedam, , Netherlands

VieCuri Medisch Centrum (Venlo)

Venlo, , Netherlands

't Lange Land Ziekenhuis

Zoetermeer, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Related Links

https://www.boogstudycenter.nl/studie/287/perideno.html

Information PERIDENO study on BOOG website (sponsor).

Other Identifiers

2016-005210-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BOOG-2017-02

Identifier Type: -

Identifier Source: org_study_id