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

NCT03691311 | Unknown Early Phase 1

• 3 other identifiers: ICO 13-0012016-002678-1120119112
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Breast Neoplasm Female; Stage I Breast Cancer; Stage II Breast Cancer; Hormone Receptor Negative Neoplasm; Hormone Receptor Positive Tumor

Keywords

rank; rankl; denosumab

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Correlation between antiproliferative activity of denosumab and Rank/RankL expression

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

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

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

• Differential antiproliferative activity of denosumab among pre and post menopausal patients

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

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

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

Other Outcomes (2)

• Changes in overall expression profile determined by RNA expression microarrays

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

• Validation of denosumab activity in clinical samples by Trap5b protein expression

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

Study Arms (2)

Denosumab

EXPERIMENTAL

Denosumab 120 MG/1.7 ML Subcutaneous Solution \[XGEVA\]

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

Control

NO INTERVENTION

Control group

Interventions

Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] DRUG

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

Denosumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and sign Informed Consent for this study.
• 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.
• 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".

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institut Català d'Oncologia: lead
• Amgen: collaborator

Study Sites (1)

Institut Català d'Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Related Publications (1)

• 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.

  PMID: 38979716 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Osteopetrosis, Autosomal Recessive 7; Osteopetrosis, mild autosomal recessive form

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: October 1, 2018
• Study Start: July 5, 2018
• Primary Completion: July 5, 2022
• Study Completion: February 5, 2023
• Last Updated: November 3, 2021

Record last verified: 2021-11

Locations

ES (1)