Abstract
BackgroundA tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue. Diffuse TGCT (D-TGCT) most commonly develops in the knee, followed by the hip, ankle, elbow, and shoulder. Surgical removal is the only effective treatment option for the patients. However, a local recurrence rate as high as 47% has been reported. Recently, we revealed that zaltoprofen, a nonsteroidal anti-inflammatory drug possessing the ability to activate peroxisome proliferator-activated receptor gamma (PPARγ), can inhibit the proliferation of TGCT stromal cells via PPARγ. PPARγ is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. It plays an important role in the differentiation of adipocytes from precursor cells and exhibits antitumorigenic effects on certain malignancies. Therefore, we are conducting this investigator-initiated clinical trial to evaluate whether zaltoprofen is safe and effective for patients with D-TGCT or unresectable localized TGCT (L-TGCT).MethodsThis study is a randomized, placebo-controlled, double-blind, multicenter trial to evaluate the safety and efficacy of zaltoprofen for patients with D-TGCT or L-TGCT. For the treatment group, zaltoprofen 480 mg/day will be administered for 48 weeks; the placebo group will receive similar dosages without zaltoprofen. Twenty participants in each group are needed in this trial (40 participants total). The primary outcome is the progression-free rate at 48 weeks after treatment administration. “Progression” is defined as any serious events (1. Repetitive joint swelling due to hemorrhage, 2. Joint range of motion limitation, 3. Invasion of adjacent cartilage or bone, 4. Severe joint space narrowing, 5. Increase in tumor size) requiring surgical interventions. We hypothesize that the zaltoprofen group will have a higher progression-free rate compared to that of the placebo group at 48 weeks.DiscussionThis is the first study to evaluate the efficacy of zaltoprofen in patients with D-TGCT or unresectable L-TGCT. We believe that the results of this trial will validate a novel treatment option, zaltoprofen, to stabilize disease progression for TGCT patients.Trial registrationUniversity Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000025901) registered on 4/01/2017.
Highlights
A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue
To the best of our knowledge, this is the first evaluation of the efficacy of zaltoprofen for patients with diffuse-type and unresectable localized TGCT by a randomized placebo-controlled double-blind phase II investigator-initiated study
Excision by arthroscopic or open synovectomy is recommended, but complete removal is sometimes difficult to achieve due to the wide spread of the growth, resulting in high local recurrence [4, 5]
Summary
A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue. A localized extra-articular TGCT, known as a giant cell tumor of the tendon sheath, commonly emerges from the smaller joints including the hand and ankle/foot. It is slight more predominant in women than in men [1] and an annual incidence has been reported as approximately one in 50,000 [2]. The recurrence rete is high despite the surgical removal An incidence of it has been reported as approximately two cases per million annually with mostly younger than 40 years and a slight female predominance [3]. Systemic therapies targeting the CSF1/CSF1R axis have been tested in patients with locally advanced or relapsed D-TGCT [7]
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