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Reduced Dose-density of Denosumab for Unresectable GCTB (REDUCE)

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ClinicalTrials.gov Identifier: NCT03620149
Recruitment Status : Not yet recruiting
First Posted : August 8, 2018
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

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.


Condition or disease Intervention/treatment Phase
Bone Giant Cell Tumor Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Dose-density of Denosumab for Maintenance Therapy of Unresectable Giant Cell Tumor of Bone: a Multicenter Phase II Study "REDUCE"
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bone Cancer
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Denosumab
denosumab at reduced dose
Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Denosumab 120 mg, SC, on day 1 of every 12-week cycle
Other Name: Xgeva




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 5.8 years after first patient in ]
    according to RECIST 1.1

  2. Osteonecrosis of the jaw (ONJ) incidence [ Time Frame: 5.8 years after first patient in ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 5.8 years after first patient in ]
  2. Denosumab treatment duration [ Time Frame: 5.8 years after first patient in ]
  3. Occurrence of Adverse Events [ Time Frame: 5.8 years after first patient in ]
    according to CTCAE v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • Bilateral tubal occlusion
  • Vasectomized partner
  • Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last study treatment.
  • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03620149


Contacts
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Contact: EORTC HQ +32 2 774 1611 1762@eortc.org

Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Amgen
Investigators
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Study Chair: Emanuela Palmerini IRCCS Instituto Ortopedico Rizzoli
Study Chair: Hans Gelderblom Leiden University Medical Center

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT03620149     History of Changes
Other Study ID Numbers: EORTC 1762-STBSG
2018-002096-17 ( EudraCT Number )
20177203 ( Other Identifier: Amgen )
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All publications must comply with the terms specified in the EORTC Policy 009 "Release of Results and Publication Policy".

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
denosumab
Giant cell tumor of bone
Additional relevant MeSH terms:
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Giant Cell Tumors
Giant Cell Tumor of Bone
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs