Reduced Dose-density of Denosumab for Unresectable GCTB

NCT03620149 | Terminated Phase 2 DMC

• 3 other identifiers: EORTC 1762-STBSG2018-002096-1720177203
• Study Type: interventional
• Target: 2
• Locations: 4 countries
• Sites: 8

Brief Summary

This study is a multi-center, multi-national, open label, single arm phase 2 study of single-agent denosumab. The objective of the trial is to evaluate the risk versus benefit of denosumab in maintenance setting in patients requiring long-term use (\> 1 year) of denosumab. For that purpose, the treatment schedule with reduced dose density (120mg SC 12-weekly instead of 4-weekly) will be investigated, starting after 1-year (12-15 months) of denosumab full dose, as per current label. The impact on OsteoNecrosis of the Jaw (ONJ) without compromising disease control will be assessed.

Conditions

Bone Giant Cell Tumor

Keywords

denosumab; Giant cell tumor of bone

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

  according to RECIST 1.1

  5.8 years after first patient in

• Osteonecrosis of the jaw (ONJ) incidence

  5.8 years after first patient in

Secondary Outcomes (3)

• Overall survival

  5.8 years after first patient in

• Denosumab treatment duration

  5.8 years after first patient in

• Occurrence of Adverse Events

  5.8 years after first patient in

Study Arms (1)

Denosumab

EXPERIMENTAL

denosumab at reduced dose

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

Interventions

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

Denosumab 120 mg, SC, on day 1 of every 12-week cycle

Also known as: Xgeva

Denosumab

Eligibility Criteria

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

You may qualify if:

• Histologically proven primary or metastatic unresectable GCTB or resectable GCTB but not a candidate for surgery, excluding primary or metastatic GCTB in the jaw.
• Evidence of active disease at time of registration based on local investigator's assessment (according to RECIST v1.1)
• Age ≥ 18 years old and skeletally mature (ie, radiographic evidence of at least 1 mature long bone (e.g. humerus with closed growth epiphyseal plate)
• Patient must have received denosumab before entering this trial:
• The duration of treatment with full dose denosumab (120 mg SC ) as per current label must be at least 12 months and patient may have received up to 15 months of denosumab.
• And patient must have received at least 12 doses of denosumab 120 mg before entering into this trial.
• ECOG/WHO PS 0-2
• Albumin-adjusted serum calcium level ≥ 2.0 mmol/L (8.0 mg/dL)
• Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review.
• Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 7 days prior to the first reduced dose of study treatment.
• WOCBP should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 5 months after the last treatment cycle. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)

You may not qualify if:

• Currently receiving other GCTB specific treatment (eg, radiation, chemotherapy, or embolization)
• Concurrent bisphosphonate treatment and calcitonin
• Known or suspected current diagnosis of underlying malignancy including high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
• Known diagnosis of second malignancy within the past 5 years (subjects with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted)
• Creatinine clearance \< 30 mL/min
• Hemoglobin \< 10.0 g/dL or 6.2 mmol/L
• Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
• Active dental or jaw condition which requires oral surgery, including tooth extraction
• Non-healed dental/oral surgery
• Planned invasive dental procedure for the course of the study
• Known hypersensitivity to the active substance or to any of the excipients (glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20)
• Treatment with other investigational device or drug 30 days prior to registration
• Known hypersensitivity to products to be administered during the study (calcium and/or vitamin D)
• Unstable systemic disease including active and uncontrolled infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before registration
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Amgen: collaborator

Study Sites (8)

IRCCS Istituto Ortopedico Rizzoli

Bologna, Italy

Location

Leiden University Medical Centre

Leiden, 2300, Netherlands

Location

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

Barcelona, 08908, Spain

Location

Vall d'Hebron Institut d'Oncologia

Barcelona, Spain

Location

Hospital Universitario San Carlos

Madrid, 28040, Spain

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, United Kingdom

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Giant Cell Tumor of Bone

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

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

Study Officials

• Emanuela Palmerini

  IRCCS Instituto Ortopedico Rizzoli

  STUDY CHAIR

• Hans Gelderblom

  Leiden University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 8, 2018
• Study Start: September 26, 2019
• Primary Completion: July 30, 2020
• Study Completion: July 30, 2020
• Last Updated: January 6, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); NL (1); ES (4); IT (1)