Breast Neoplasms Clinical Trial
— PERIDENOOfficial 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
Verified date | July 2019 |
Source | Borstkanker Onderzoek Groep |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | June 2023 |
Est. primary completion date | February 2021 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Netherlands | 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 |
Lead Sponsor | Collaborator |
---|---|
Borstkanker Onderzoek Groep | Amgen |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment. | |
Primary | 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. | The change can be determined after the surgical specimen is obtained, which is around two weeks after enrolment. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | 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. | 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. | |
Secondary | Correlation of tumor measurements with serum measurements. | Measurements in tumor and serum will be correlated. | 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. | |
Secondary | Correlation of tumor measurements with PBMCs measurements. | Measurements in tumor and PBMCs will be correlated. | 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. | |
Secondary | Correlation of serum measurements and PBMCs measurements. | Measurements in serum and PBMCs will be correlated. | 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. | |
Secondary | Toxicity according to NCI CTCAE v4.03. | Toxicities are graded according to NCI CTCAE v4.03. | Toxicity will be assessed from start treatment up to 30 days following the last dose of treatment. | |
Secondary | 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. | EFS will be determined after 3 years. |
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