GCTPhase 2NCT00396279
Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
A Phase 2 study testing Denosumab and Calcium/Vitamin D in people with GCT and Giant Cell Tumor of Bone, run by Amgen.
Trial summary
To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GCT, Giant Cell Tumor of Bone
- What is being tested?
- Denosumab and Calcium/Vitamin D
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- No sites listed yet
- Study dates
- 10 Jul 2006to 1 Feb 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults, 18 years and older
- Histologically confirmed and measurable giant cell tumor (GCT)
- Recurrent GCT confirmed by radiology or unresectable GCT
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Who cannot join
- Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
- Radiation to affected region within 28 days before enrollment to study
- Known diagnosis of osteosarcoma or brown tumor of bone
- Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
- Concurrent treatment with bisphosphonates, calcitonin, or interferon.
- Other criteria also apply.
About this study
Official title: An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone
To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.
- Conditions
- GCT, Giant Cell Tumor of Bone
- Being tested
- Denosumab, Calcium/Vitamin D
- Keywords
- Giant Cell Tumor of Bone
- Medical subject headings
- Giant Cell Tumor of Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabBiological
Also called Xgeva®
Administered by subcutaneous injection
Calcium/Vitamin DDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Denosumab | Experimental | Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. Receives: Biological: Denosumab; Dietary Supplement: Calcium/Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Giant Cell Tumor Response
A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
Measured: From enrollment until 25 weeks
Secondary outcomes (5)
Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
Measured: Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
Measured: Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Serum Denosumab Trough Concentrations
Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
Measured: Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.
Number of Participants With Adverse Events (AEs)
An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
Measured: From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months
Number of Participants With Anti-Denosumab Antibodies
Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.
Measured: From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2006 (estimated)
- Study start10 Jul 2006
- Primary completion7 Apr 2008
- Study completion1 Feb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for GCTStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00396279
- Sponsor's protocol ID
- 20040215
- Status last verified
- Nov 2022
- First submitted
- 2 Nov 2006
- Last updated
- 8 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18.
PubMed 22711702Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.
PubMed 20149736Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3.
PubMed 30231890
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone
- ClinicalTrials.gov ID
- NCT00396279
- Acronym / sponsor ID
- 20040215
- Conditions
- GCT, Giant Cell Tumor of Bone
- Keywords
- Giant Cell Tumor of Bone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 10 Jul 2006 (actual)
- Primary completion
- 7 Apr 2008 (actual)
- Study completion
- 1 Feb 2011 (actual)
- First posted
- 6 Nov 2006 (estimated)
- Results
- Posted 5 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Experimental | Biological: Denosumab, Dietary Supplement: Calcium/Vitamin DParticipants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults, 18 years and older
- Histologically confirmed and measurable giant cell tumor (GCT)
- Recurrent GCT confirmed by radiology or unresectable GCT
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Key exclusion criteria (6 listed)
- Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
- Radiation to affected region within 28 days before enrollment to study
- Known diagnosis of osteosarcoma or brown tumor of bone
- Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
- Concurrent treatment with bisphosphonates, calcitonin, or interferon.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: Xgeva®Administered by subcutaneous injection | Biological | Denosumab |
| Calcium/Vitamin D | Dietary supplement | Denosumab |
Primary outcome
Percentage of Participants With Giant Cell Tumor Response
Time frame: From enrollment until 25 weeks
A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
5 secondary outcomes
Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
Time frame: Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
Time frame: Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Serum Denosumab Trough Concentrations
Time frame: Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.
Number of Participants With Adverse Events (AEs)
Time frame: From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months
Number of Participants With Anti-Denosumab Antibodies
Time frame: From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22711702Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18.
- Background: PubMed 20149736Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.
- Derived from this study: PubMed 30231890Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab and Calcium/Vitamin D in people with GCT and Giant Cell Tumor of Bone, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Giant Cell Tumor Response (time frame: From enrollment until 25 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00396279, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.