Aneurysmal Bone Cysts Clinical Trial
Official title:
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).
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
;