Denosumab in Subjects With Giant Cell Rich Tumors of Bone

August 22, 2019 updated by: HansGelderblom, Leiden University Medical Center

An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Rich Tumors of Bone

An open-label, multi-center, phase 2 study of the efficacy of denosumab in subjects with giant cell rich tumors of bone. The population will consist of subjects with the following tumor types: aneurysmal bone cysts (ABC), giant cell granuloma (GCG) and other giant cell rich lesions (primary bone, non-malignant).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this phase 2 single arm trial subjects with giant cell rich tumors that would require morbid surgery OR with tumors that have recurred after previous surgery will be treated with denosumab. The primary objectives of the study are to evaluate avoidance of surgery and performance of less morbid surgical procedure compared with the planned surgical procedure at baseline in subjects with salvageable giant cell rich tumors during the study. For subjects with unsalvageable tumors the objective is to evaluate disease control (radiological response assessed by combined RECIST, PET, inverse Choi when available and/or no progression at 1 year (based on disease assessment) in combination with stable pain score defined as ≤ 1 point increase on 'worst pain' question in BPI-SF).

Surgical resection may occur at any time during the study based on the clinical judgement of the Investigator. For subjects that undergo surgical tumor resection, denosumab treatment will be discontinued after surgery. In all other cases, denosumab treatment continues for a maximum of up to 3 years, or until confirmation of disease progression, the Investigator's or Sponsor's recommendation of discontinuation, the subject's decision to discontinue for any reason or administration of any of the prohibited therapies listed in the study protocol. For subjects that continue to show clinical benefit after 3 years of treatment with denosumab, ongoing treatment outside of study protocol is optional after discussion with Amgen.

For assessment of histopathological response and for translational research purposes a tumor sample will be requested either during study or at the EOT (surgical sample only for the subject group that has undergone surgery).

During the time the study is still open, re-treatment may be allowed for subjects who demonstrated a response to denosumab and are currently not receiving denosumab treatment (e.g., in the case of recurrent disease while subject is in the safety follow-up phase or subjects that have completed the study and have later experienced disease progression). The re-treatment decision including the use of the loading dose and discontinuation of therapy will be handled on a case-by-case basis; prior authorization from the Sponsor is required. Subjects must meet all inclusion/exclusion criteria prior to being considered for re-treatment, with the exception of the exclusion criterium of previous denosumab treatment. The same subject number will be assigned to avoid bias.

Overall in total approximately 60 subjects with giant cell rich tumors that would require morbid surgery or with tumors that have recurred after previous surgery will be included. The investigators expect 50% of subjects will have salvageable giant cell rich tumors and the remaining 50% of subjects to have unsalvageable giant cell rich tumors.

The population will consist of subjects with the following cohorts according to tumor type:

  • Aneurysmal bone cysts (ABC), ~ approximately 40 subjects
  • Giant Cell Granuloma (GCG) and other giant cell rich lesions (primary bone, non-malignant), ~ approximately 20 subjects

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: AJ Gelderblom
  • Phone Number: +31715269111

Study Locations

  • France
      • Lyon, France
        • Not yet recruiting
        • Centre Leon Berard
        • Contact:
          • JY Blay
  • Italy
      • Bologna, Italy
        • Not yet recruiting
        • Istituto Ortopedico Rizzoli
        • Contact:
          • E Palmerini
  • Netherlands
      • Leiden, Netherlands
        • Recruiting
        • Leiden University Medical Center
        • Contact:
          • H Gelderblom, Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically proven giant cell rich tumor:

    • Aneurysmal bone cysts (ABC)
    • Giant cell granuloma (GCG)
    • Other giant cell rich lesions (primary bone, non-malignant, pathology and radiology to be reviewed during multidisciplinary meeting LUMC)
  • Patients with surgically unsalvageable disease (e.g., sacral, spinal giant cell rich tumors, or multiple lesions including pulmonary metastases) OR patients whose planned surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity
  • Measurable evidence of active disease within 1 year before study enrollment
  • Albumin-adjusted serum calcium level ≥ 2.0 mmol/L (8.0 mg/dL)
  • Aged 18 years and up and skeletally mature
  • ECOG performance status 0, 1 or 2
  • Written signed informed consent

Exclusion Criteria:

  • Known or suspected current diagnosis of classic GCTB
  • Known or suspected current diagnosis of underlying malignancy including but not limited to high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
  • Known or suspected current diagnosis of brown cell tumor of hyperparathyroidism, Paget's disease or cherubism
  • Known or suspected current diagnosis of primary soft tissue tumor with invasion of the bone
  • Known diagnosis of other malignancy within the past 5 years (patients with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted)
  • Previous treatment with denosumab (with the exception of patients eligible for re-treatment with denosumab after completing this study)
  • 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 denosumab
  • Known hypersensitivity to products to be administered during the study (calcium and/or vitamin D)
  • Currently receiving other specific treatment for giant cell rich tumors of bone (e.g., radiation, chemotherapy or embolization)
  • Concurrent bisphosphonate treatment
  • Major surgery less than 4 weeks prior to start of treatment
  • Treatment with other investigational device or drug 30 days prior to study enrollment
  • Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollment
  • Patient is pregnant or breast feeding, or planning to become pregnant within 5 months after the EOT visit
  • Female patient of child bearing potential is not willing to use a highly effective method of contraception during treatment and for 5 months after the EOT visit
  • Patient has any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Denosumab active treatment
Drug: Denosumab
Denosumab will be given in a dose of 120mg subcutaneously (SC) on day 1 of every 4 week cycle with a loading dose of 120mg SC on days 8 and 15 of the first cycle.
Other Names:
  • Xgeva

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy (proportion of subjects who do not require surgery during the study)
Time Frame: Continuous monitoring until surgery of max treatment duration of 3 years.
(For subgroup of subjects with salvageable tumors):The proportion of subjects who do not require surgery during the study.
Continuous monitoring until surgery of max treatment duration of 3 years.
Efficacy (proportion of subjects undergoing the planned versus performed type of surgery during the study)
Time Frame: Continuous monitoring until surgery of max treatment duration of 3 years.
(For subgroup of subjects with salvageable tumors): The proportion of subjects undergoing the planned versus performed type of surgery during the study.
Continuous monitoring until surgery of max treatment duration of 3 years.
Efficacy (Radiological response)
Time Frame: Imaging to be performed every 3 months. Up to maximum duration of treatment of 3 years.

(For subgroup of subjects with UNsalvageable tumors) Combined endpoint: 1. Disease control:

o Radiological response assessed by combined RECIST, PET, inverse Choi criteria when available
Imaging to be performed every 3 months. Up to maximum duration of treatment of 3 years.
Efficacy (disease progression based on clinical disease assessment)
Time Frame: Clinical disease assessment performed every 4 weeks. Up to maximum duration of treatment of 3 years.

(For subgroup of subjects with UNsalvageable tumors) Combined endpoint: 2. Disease control:

o No progression at 1 year (based on clinical disease assessment)
Clinical disease assessment performed every 4 weeks. Up to maximum duration of treatment of 3 years.
Efficacy (combined pain scores)
Time Frame: Questionnaires on pain to be performed every 4 weeks. Up to maximum duration of treatment of 3 years.
(For subgroup of subjects with UNsalvageable tumors) Combined endpoint: 3. Stable pain score, defined as ≤ 1 point increase on 'worst pain' question in Brief Pain Inventory - Short Form (BPI-SF, measures pain severity on a scale of 0 to 10 [10 being worse pain], and pain interference on a scale of 0 to 10 [10 being complete interference], scores are averaged in total test score).
Questionnaires on pain to be performed every 4 weeks. Up to maximum duration of treatment of 3 years.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Toxicity according to CTCAE v 4.03
Time Frame: Assessed every 4 weeks up to 3 years.
- Frequency of adverse events (AEs), as determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 criteria
Assessed every 4 weeks up to 3 years.
Disease recurrence after denosumab followed by surgery.
Time Frame: Follow-up every 6-12 months after end of treatment, up to 5 years max.
The proportion of subjects with disease recurrence after denosumab followed by surgery during the study.
Follow-up every 6-12 months after end of treatment, up to 5 years max.
Symptomatic improvement.
Time Frame: Questionnaires to be performed every 4 weeks during first 6 months on treatment, after 6 months assessment is every 12 weeks. Up to 3 years.
Symptomatic improvement in the Brief Pain Inventory - Short Form (BPI-SF, measures pain severity on a scale of 0 to 10 [10 being worse pain], and pain interference on a scale of 0 to 10 [10 being complete interference], scores are averaged in total test score).
Questionnaires to be performed every 4 weeks during first 6 months on treatment, after 6 months assessment is every 12 weeks. Up to 3 years.
Symptomatic improvement.
Time Frame: Questionnaires to be performed every 4 weeks during first 6 months on treatment, after 6 months assessment is every 12 weeks. Up to 3 years.
Symptomatic improvement in the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC QLC-30, 28 questions regarding interference of disease with QoL ranging from 1 'not at all' to 4 'very much', 2 questions regarding QoL raging from 1 'very poor' to 7 'excellent', scores are averaged in total test score)
Questionnaires to be performed every 4 weeks during first 6 months on treatment, after 6 months assessment is every 12 weeks. Up to 3 years.
Time to surgery
Time Frame: Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years.
Time in months
Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years.
Time to recurrence after surgery (for patients with salvageable disease)
Time Frame: Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years
Time in months
Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years
Progression free survival
Time Frame: Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years
Time in months
Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years
Overall survival.
Time Frame: Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years
Time in months
Continuous monitoring, clinical assessment every 4 weeks during treatment and every 6-12 months after end of treatment up to max of 5 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Translational research.
Time Frame: Pathology samples once during study or at end of treatment (surgery), max duration of 3 years.
Translational research on tumor material, including proportion of subjects with pathological response for subjects undergoing surgery.
Pathology samples once during study or at end of treatment (surgery), max duration of 3 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Leiden University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: AJ Gelderblom, Prof, Leiden University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 18, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 26, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20159990

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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