Clinical Trials /

Reduced Dose-density of Denosumab for Unresectable GCTB

NCT03620149

Description:

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.

Related Conditions:
  • Malignancy in Giant Cell Tumor of Bone
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Reduced Dose-density of Denosumab for Unresectable GCTB
  • Official Title: Reduced Dose-density of Denosumab for Maintenance Therapy of Unresectable Giant Cell Tumor of Bone: a Multicenter Phase II Study "REDUCE"

Clinical Trial IDs

  • ORG STUDY ID: EORTC 1762-STBSG
  • SECONDARY ID: 2018-002096-17
  • SECONDARY ID: 20177203
  • NCT ID: NCT03620149

Conditions

  • Bone Giant Cell Tumor

Interventions

DrugSynonymsArms
Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]XgevaDenosumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DenosumabExperimentaldenosumab at reduced dose
  • Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:5.8 years after first patient in
Safety Issue:
Description:according to RECIST 1.1

Secondary Outcome Measures

Measure:Overall survival
Time Frame:5.8 years after first patient in
Safety Issue:
Description:
Measure:Denosumab treatment duration
Time Frame:5.8 years after first patient in
Safety Issue:
Description:
Measure:Occurrence of Adverse Events
Time Frame:5.8 years after first patient in
Safety Issue:
Description:according to CTCAE v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Trial Keywords

  • denosumab
  • Giant cell tumor of bone

Last Updated

December 24, 2019