Pilot Study to Evaluate the Impact of Denosumab on Disseminated Tumor Cells (DTC) in Patients With Early Stage Breast Cancer

NCT01545648 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 117527NCI-2012-02802
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see whether taking denosumab for 12 months in women with a significant number of disseminated tumor cells in the bone marrow can reduce the number of these cells below a significant level.

Conditions

Early Stage Breast Cancer

Keywords

breast; cancer; early; DTC; disseminated; tumor; cells

Outcome Measures

Primary Outcomes (2)

• Percentage of Change in Reduction of Disseminated Tumor Cells (DTC)/Mililitre (ml)

  Reduction of disseminated tumor cells (DTC)/ mililitre (ml) from \>10DTC/ml to ≤ 10DTC/ml. DTC measured by IE/FC in patients with early stage

  Up to 12 months

• Disseminated Tumor Cell Counts

  Changes from baseline in disseminated tumor cell counts

  Up to 12 months

Secondary Outcomes (1)

• Correlation of Local Recurrence With DTC

  Up to 12 months

Study Arms (1)

denosumab

EXPERIMENTAL

Dosage: 120 mg, monthly for total of 6 months, then every 12 weeks for 2 doses, for a total treatment course of one year Route of administration: subcutaneous injection

Drug: Denosumab

Interventions

Denosumab DRUG

Formulation of Dosage forms The vial presentations of denosumab contain 60 mg/mL denosumab, 17 mM sodium acetate, and 4.7% (w/v) sorbitol, at a pH of 5.2, filled to a target deliverable volume of 1.0 mL; or 70 mg/mL denosumab, 18 mM sodium acetate and 4.6% (w/v) sorbitol, at a pH of 5.2, filled to a target deliverable volume of 1.7 mL. The prefilled syringe (PFS) drug product contains denosumab at 60 mg/mL, 17 mM sodium acetate, 4.7% (w/v) sorbitol, and 0.01% (w/v) polysorbate 20, at a pH of 5.2, filled to a target deliverable volume of 1.0 mL. Dosage: 120 mg, monthly for total of 6 months, then every 12 weeks for 2 doses, for a total treatment course of one year Route of administration: subcutaneous injection

Also known as: AMG 162, XGEVA™, Prolia®

denosumab

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years of age with histologically or cytologically confirmed stage I, II, or III breast cancer.
• ECOG Performance Status of 0 or 1
• Prior therapy:
• Prior adjuvant therapy is not required for participation in this study.
• If adjuvant or neoadjuvant treatment with chemotherapy is recommended, it must be completed before study start, and not more than 18 months prior to study start.
• If adjuvant or neoadjuvant treatment with trastuzumab (Herceptin®) is recommended, patients should have received at least 3 months of therapy before eligibility bone marrow is performed.
• Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible
• Patients must have completed definitive surgery and have completely resected disease.
• Concomitant hormonal therapy is allowed.
• Concomitant adjuvant trastuzumab is permitted
• If adjuvant hormonal treatment is recommended, patients should have received at least 3 months of therapy before screening bone marrow is performed.
• Bone marrow aspirate positive by IE/FC assay within 12 weeks of study entry
• Definition of positive: \>10 DTC/ml
• Timing of bone marrow aspiration to determine study eligibility
• i.If patient is to receive either no adjuvant therapy or hormonal therapy alone, the aspiration may be performed at diagnosis as part of the large micrometastasis study at UCSF, or following diagnosis if the patient received initial surgery elsewhere. This is also true for patients who have surgery following neoadjuvant therapy for breast cancer.

You may not qualify if:

• Karnofsky performance status \< 90%
• Patients participating in this study are not allowed to receive bisphosphonate therapy during the study period, either oral or intravenous.
• Patients who completed adjuvant or neoadjuvant therapy more than 18 months prior to study screening.
• A history of malignancy within the last 5 years except basal cell carcinoma of skin.
• A history of human immunodeficiency virus (HIV) infection.
• Severe, concurrent illness that would likely prevent the patient from being able to comply with the study protocol.
• Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control.
• Significant dental disease that requires major intervention during the study period, such as tooth extraction
• Significant coagulopathy that would prevent safe bone marrow aspiration

Sponsors & Collaborators

• Hope Rugo, MD: lead
• University of California, San Francisco: collaborator
• Amgen: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Stefanovic S, Diel I, Sinn P, Englert S, Hennigs A, Mayer C, Schott S, Wallwiener M, Blumenstein M, Golatta M, Heil J, Rom J, Sohn C, Schneeweiss A, Schuetz F, Domschke C. Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: Prognostic Impact in Immunophenotypic Subgroups and Clinical Implication for Bisphosphonate Treatment. Ann Surg Oncol. 2016 Mar;23(3):757-66. doi: 10.1245/s10434-015-4895-3. Epub 2015 Oct 14.

  PMID: 26467455 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Study terminated early due to low accrual

Results Point of Contact

• Title: Hope Rugo, MD
• Organization: University of California, San Francisco

cancertrials@ucsf.edu

877-827-3222

Study Officials

• Hope Rugo, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: February 27, 2012
• First Posted: March 7, 2012
• Study Start: November 1, 2012
• Primary Completion: June 9, 2015
• Study Completion: June 9, 2016
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)