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REDUCE: Reduced Dose-density of Denosumab for Unresectable GCTB

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC (Other)
Overall Status
Terminated
CT.gov ID
NCT03620149
Collaborator
Amgen (Industry)
2
Enrollment
8
Locations
1
Arm
10.1
Actual Duration (Months)
0.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
  • Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
N/A
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"
Actual Study Start Date :
Sep 26, 2019
Actual Primary Completion Date :
Jul 30, 2020
Actual Study Completion Date :
Jul 30, 2020

Arms and Interventions

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 Names:
  • Xgeva

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression free survival (PFS) [5.8 years after first patient in]

      according to RECIST 1.1

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

    Secondary Outcome Measures

    1. Overall survival [5.8 years after first patient in]

    2. Denosumab treatment duration [5.8 years after first patient in]

    3. Occurrence of Adverse Events [5.8 years after first patient in]

      according to CTCAE v5.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
    2 Leiden University Medical Centre Leiden Netherlands 2300
    3 Hospital De La Santa Creu I Sant Pau Barcelona Spain 08041
    4 Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia) Barcelona Spain 08908
    5 Vall d'Hebron Institut d'Oncologia Barcelona Spain
    6 Hospital Universitario San Carlos Madrid Spain 28040
    7 University College London Hospitals NHS Foundation Trust - University College Hospital London United Kingdom
    8 Oxford University Hospitals NHS Trust - Churchill Hospital Oxford United Kingdom OX3 7LE

    Sponsors and Collaborators

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

    Investigators

    • Study Chair: Emanuela Palmerini, IRCCS Instituto Ortopedico Rizzoli
    • Study Chair: Hans Gelderblom, Leiden University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    European Organisation for Research and Treatment of Cancer - EORTC
    ClinicalTrials.gov Identifier:
    NCT03620149
    Other Study ID Numbers:
    • EORTC 1762-STBSG
    • 2018-002096-17
    • 20177203
    First Posted:
    Aug 8, 2018
    Last Update Posted:
    Jan 6, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Giant Cell Tumors
    Giant Cell Tumor of Bone
    Denosumab

    Study Results

    No Results Posted as of Jan 6, 2021