Denosumab in Subjects With Giant Cell Rich Tumors of Bone

NCT03605199 | Unknown Phase 2

• 1 other identifier: 20159990
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 3

Brief Summary

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).

Conditions

Aneurysmal Bone Cysts; Giant Cell Granuloma; Osteoblastoma; Chondroblastoma; Chondromyxoid Fibroma

Keywords

denosumab; giant cell rich tumor of bone

Outcome Measures

Primary Outcomes (5)

• Efficacy (proportion of subjects who do not require surgery during the study)

  (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)

  (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)

  (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)

  (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)

  (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 Outcomes (8)

• Toxicity according to CTCAE v 4.03

  Assessed every 4 weeks up to 3 years.

• Disease recurrence after denosumab followed by surgery.

  Follow-up every 6-12 months after end of treatment, up to 5 years max.

• Symptomatic improvement.

  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.

  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

  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 Outcomes (1)

• Translational research.

  Pathology samples once during study or at end of treatment (surgery), max duration of 3 years.

Study Arms (1)

Denosumab active treatment

EXPERIMENTAL

Denosumab active treatment

Drug: Denosumab

Interventions

Denosumab DRUG

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.

Also known as: Xgeva

Denosumab active treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Amgen: collaborator

Study Sites (3)

Centre Léon Bérard

Lyon, France

NOT YET RECRUITING

Istituto Ortopedico Rizzoli

Bologna, Italy

NOT YET RECRUITING

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

Related Publications (1)

• Lipplaa A, Schreuder WH, Pichardo SEC, Gelderblom H. Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study. Oncologist. 2023 Nov 2;28(11):1005-e1104. doi: 10.1093/oncolo/oyad196.

  PMID: 37449658 DERIVED

MeSH Terms

Conditions

Bone Cysts, Aneurysmal; Granuloma, Giant Cell; Osteoblastoma; Chondroblastoma

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Cysts; Cysts; Neoplasms; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Gingival Diseases; Periodontal Diseases; Mouth Diseases; Granuloma; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• AJ Gelderblom, Prof

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

A Lipplaa, MD

CONTACT

a.lipplaa@lumc.nl

AJ Gelderblom

CONTACT

+31715269111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 30, 2018
• Study Start: June 18, 2018
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2023
• Last Updated: August 26, 2019

Record last verified: 2019-08

Locations

NL (1); IT (1); FR (1)