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CompletedNCT03301857Updated May 20, 2024Results posted

Long-term Safety Follow-up of Subjects With Giant Cell Tumor of Bone Treated With Denosumab in Study 20062004

A Phase 4 interventional study of Denosumab in Giant Cell Tumor of Bone, sponsored by Amgen. Completed at 14 sites in 8 countries. Per ClinicalTrials.gov, last updated 2024-05-20.

Sponsored by Amgen · Phase 4, Interventional, and Supportive care

Phase
Phase 4
Study type
Interventional
Enrollment
85
Allocation
Non-randomized
Sex
All
01

Study summary

Study 20140114 will continue to follow participants with GCTB who were treated in Study 20062004 and remained on the study at the completion of Study 20062004 for an additional 5 years on long-term safety follow up.

Read the detailed description

Study 20140114 will continue to follow participants with GCTB who were treated in Study 20062004 and remained on the study at the completion of Study 20062004 for an additional 5 years on long-term safety follow up. Collection of long-term safety information will include adverse events of interest and all treatment-emergent adverse events and serious adverse events

02

Conditions studied

03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participant was previously enrolled in Study 20062004.
  • Participant or participant's legally acceptable representative has provided informed consent/assent prior to initiation of any study-specific activities/procedures.

Exclusion criteria

Exclusion Criteria:

  • Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
  • Females of childbearing potential on denosumab and not willing to continue to use 1 highly effective method of contraception during treatment and for 5 months after the end of treatment
04

Study design

Phase
Phase 4
Primary purpose
Supportive care
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
85 participants (actual)

Study arms

  • Experimental
    Denosumab

    Participants who are still being treated with denosumab when 20062004 completes: 120 mg administered subcutaneously (SC) every 4 weeks (Q4W). For participants undergoing retreatment with denosumab: 120 mg administered SC on Days 1, 8, 15 and 28 then every 4 weeks subsequently.

    Drug: Denosumab

  • No intervention
    Safety Follow-up

    Participants who completed denosumab treatment and were in safety follow-up at the conclusion of 20062004 will have follow-up visits performed every 6 months via telephone or in-person clinic visit.

Interventions

  • DrugDenosumab

    120 mg administered subcutaneously (SC) every 4 weeks (Q4W).

    Also known as: AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand

05

What researchers measure

Primary outcomes

  1. Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI)

    EOIs assessed in the study were signs and symptoms of osteonecrosis of the jaw (ONJ), malignancy (including malignancy in GCTB), atypical femoral fracture (AFF), hypocalcemia, hypercalcemia after treatment discontinuation, pregnancy and lactation (if occurring during treatment or within 5 months of the last dose of denosumab). Hypocalcemia includes events that occurred after 30 days following the last dose of IP and includes TEAEs only. Other EOIs encompass all events from signing the informed consent to the end of the study (approximately 5 years). ONJ and AFF events were adjudicated by independent reviewers.

    Time frame: Up to approximately 5 years

Secondary outcomes

  1. Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)

    An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. An AE is considered as treatment-emergent if the AE occurs during the time period from the first dose of IP in this study through last dose of IP plus 30 days. TEAEs related to IP include only TEAEs for which the Investigator indicated there was a reasonable possibility they may have been caused by IP. AEs were graded (grade 3 \[severe or medically significant but not immediately life-threatening\], 4 \[life-threatening\], and 5 \[death related to the AE\]) using the Common Terminology Criteria for Adverse Events (CTCAE).

    Time frame: Up to approximately 5 years

  2. Number of Participants With Disease Progression or Recurrence of GCTB

    Disease progression or recurrence is defined as the best post-baseline response of progressive disease (PD) without any post-baseline complete response (CR) /partial response (PR) /stable disease (SD) or a post-baseline response of PD following a post-baseline CR/PR/SD. PD is defined as the response of progressive disease, locally recurrent disease or distant recurrence. CR is defined as no evidence of disease following surgical resection while on study 20062004. PR is defined as no new lesion or disease progression while enrolled in study 20062004. SD is defined as local disease progression/recurrence or distant metastatic disease while on study 20062004.

    Time frame: Up to approximately 5 years

  3. Number of Participants Receiving GCTB Interventions

    GCTB interventions include: surgery, chemotherapy, embolization, interferon, and radiotherapy.

    Time frame: Up to approximately 5 years

06

Results

Posted May 20, 2024

Participant flow

Participants with giant cell tumor of bone (GCTB) were enrolled across 8 countries (Australia, Italy, France, Poland, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States) between November 2017 and July 2023.

Participant flow — Overall Study
MilestoneExposed to Investigational Product (IP)Not Exposed to IP
Started5134
Received denosumab510
Completed2926
Not completed228
Withdrew: Death02
Withdrew: Lost to follow-up42
Withdrew: Decision by sponsor60
Withdrew: Withdrawal by subject124

Outcome measures

PrimaryNumber of Participants Experiencing Adverse Events (AEs) of Interest (EOI)

EOIs assessed in the study were signs and symptoms of osteonecrosis of the jaw (ONJ), malignancy (including malignancy in GCTB), atypical femoral fracture (AFF), hypocalcemia, hypercalcemia after treatment discontinuation, pregnancy and lactation (if occurring during treatment or within 5 months of the last dose of denosumab). Hypocalcemia includes events that occurred after 30 days following the last dose of IP and includes TEAEs only. Other EOIs encompass all events from signing the informed consent to the end of the study (approximately 5 years). ONJ and AFF events were adjudicated by independent reviewers.

Time frame:
Up to approximately 5 years
Reported as:
Number · Count of Participants
Number of Participants Experiencing Adverse Events (AEs) of Interest (EOI)
Count of ParticipantsExposed to IPNot Exposed to IP
Adjudicated positive ONJ30
Malignancy, including malignancy in GCTB61
Adjudicated positive AFF20
Hypocalcemia30
Hypocalcemia after treatment end00
Pregnancy and lactation00
SecondaryNumber of Participants Experiencing Treatment-emergent Adverse Events (TEAE)

An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. An AE is considered as treatment-emergent if the AE occurs during the time period from the first dose of IP in this study through last dose of IP plus 30 days. TEAEs related to IP include only TEAEs for which the Investigator indicated there was a reasonable possibility they may have been caused by IP. AEs were graded (grade 3 \[severe or medically significant but not immediately life-threatening\], 4 \[life-threatening\], and 5 \[death related to the AE\]) using the Common Terminology Criteria for Adverse Events (CTCAE).

Time frame:
Up to approximately 5 years
Reported as:
Number · Count of Participants
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
Count of ParticipantsExposed to IP
All TEAEs47
Serious TEAEs8
Fatal TEAEs0
TEAEs leading to IP discontinuation9
CTCAE Grade 3, 4, or 516
All TEAEs related to IP14
SecondaryNumber of Participants With Disease Progression or Recurrence of GCTB

Disease progression or recurrence is defined as the best post-baseline response of progressive disease (PD) without any post-baseline complete response (CR) /partial response (PR) /stable disease (SD) or a post-baseline response of PD following a post-baseline CR/PR/SD. PD is defined as the response of progressive disease, locally recurrent disease or distant recurrence. CR is defined as no evidence of disease following surgical resection while on study 20062004. PR is defined as no new lesion or disease progression while enrolled in study 20062004. SD is defined as local disease progression/recurrence or distant metastatic disease while on study 20062004.

Time frame:
Up to approximately 5 years
Reported as:
Number · Count of Participants
Number of Participants With Disease Progression or Recurrence of GCTB
Count of ParticipantsExposed to IPNot Exposed to IP
Number of Participants With Disease Progression or Recurrence of GCTB53
SecondaryNumber of Participants Receiving GCTB Interventions

GCTB interventions include: surgery, chemotherapy, embolization, interferon, and radiotherapy.

Time frame:
Up to approximately 5 years
Reported as:
Number · Count of Participants
Number of Participants Receiving GCTB Interventions
Count of ParticipantsExposed to IPNot Exposed to IP
Surgery for GCTB13
Chemotherapy or Other Therapeutic Agents02
Embolization00
Interferon00
Radiotherapy00

Adverse events

Collected over Up to Approximately 5 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Exposed to IP0/51 (0%)8/51 (15.7%)37/51 (72.5%)
Not Exposed to IP2/34 (5.9%)0/34 (0%)0/34 (0%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventExposed to IPNot Exposed to IP
Femur fractureInjury, poisoning and procedural complications2/510/34
AnaemiaBlood and lymphatic system disorders1/510/34
Anal fistulaGastrointestinal disorders1/510/34
Gastrointestinal obstructionGastrointestinal disorders1/510/34
Medical device site infectionInfections and infestations1/510/34
SepsisInfections and infestations1/510/34
Viral pericarditisInfections and infestations1/510/34
Patella fractureInjury, poisoning and procedural complications1/510/34
MyositisMusculoskeletal and connective tissue disorders1/510/34
Osteonecrosis of jawMusculoskeletal and connective tissue disorders1/510/34
Most frequent other events
Showing 10 of 16
Most frequent other events
EventExposed to IPNot Exposed to IP
ToothacheGastrointestinal disorders8/510/34
ArthralgiaMusculoskeletal and connective tissue disorders8/510/34
Pain in extremityMusculoskeletal and connective tissue disorders8/510/34
COVID-19Infections and infestations7/510/34
Back painMusculoskeletal and connective tissue disorders7/510/34
Osteonecrosis of jawMusculoskeletal and connective tissue disorders6/510/34
CoughRespiratory, thoracic and mediastinal disorders5/510/34
AnaemiaBlood and lymphatic system disorders4/510/34
Foot fractureInjury, poisoning and procedural complications4/510/34
MyalgiaMusculoskeletal and connective tissue disorders4/510/34

Baseline characteristics

Full analysis set (FAS) included all enrolled participants (from study 20062004) who provided informed consent and had a non-missing enrolment date in this study.

Age, Continuous
Age, Continuous(Years)Exposed to IPNot Exposed to IPTotal
Mean42.4 ± 12.846.7 ± 15.144.1 ± 13.9
Sex: Female, Male
Sex: Female, Male(Participants)Exposed to IPNot Exposed to IPTotal
Female322355
Male191130
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Exposed to IPNot Exposed to IPTotal
Hispanic or Latino131023
Not Hispanic or Latino382462
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Exposed to IPNot Exposed to IPTotal
White353166
Other10010
Black (or African American)437
Asian202
07

Study locations

14 sites
  • Sarcoma Oncology Research Center LLC
    Santa Monica, California 90403, United States
  • Washington Cancer Institute at MedStar Washington Hospital
    Washington, District of Columbia 20010, United States
  • University of Minnesota Medical Center Fairview
    Minneapolis, Minnesota 55455, United States
  • Mount Sinai Beth Israel Downtown
    New York, New York 10003, United States
  • Abramson Cancer Center at Pennsylvania Hospital
    Philadelphia, Pennsylvania 19106, United States
  • Royal Prince Alfred Hospital
    Camperdown, New South Wales 2050, Australia
  • Centre Leon Berard
    Lyon CEDEX 08, 69373, France
  • Institut Gustave Roussy
    Villejuif, 94805, France
  • Istituti Ortopedici Rizzoli
    Bologna, 40136, Italy
  • Instytut Matki i Dziecka
    Warszawa, 01-211, Poland
  • Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie â€" Panstwowy Instytut Badawczy
    Warszawa, 02-781, Poland
  • Hospital Universitari Son Espases
    Palma de Mallorca, Baleares 07010, Spain
  • Skane Universitetssjukhus
    Lund, 221 85, Sweden
  • Royal Orthopaedic Hospital
    Birmingham, B31 2AP, United Kingdom
08

References and documents

Study documents

  • Study protocol · Aug 23, 2018
  • Statistical analysis plan · Sep 4, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03301857
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Oct 4, 2017
Start date
Nov 13, 2017
Primary completion
Jul 27, 2023
Completion
Jul 27, 2023
Results posted
May 20, 2024
Last update
May 20, 2024

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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