Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: A study protocol

Akihiko Takeuchi, Akihiro Nomura, Norio Yamamoto, Katsuhiro Hayashi, Kentaro Igarashi, Susumu Tandai, Akira Kawai, Akihiko Matsumine, Shinji Miwa, Yoshihiro Nishida, Tomoki Nakamura, Ryu Terauchi, Manabu Hoshi, Toshiyuki Kunisada, Makoto Endo, Kenichi Yoshimura, Toshinori Murayama, Hiroyuki Tsuchiya

Research output: Contribution to journalArticle

Abstract

Background: A 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). Methods: This 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. Discussion: This 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 registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000025901) registered on 4/01/2017.

Original languageEnglish
Article number68
JournalBMC Musculoskeletal Disorders
Volume20
Issue number1
DOIs
Publication statusPublished - Feb 9 2019

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Placebos
PPAR gamma
Joints
Pigmented Villonodular Synovitis
Clinical Trials
Neoplasms
Information Services
pyranoprofen
Giant Cell Tumor of Tendon Sheath
Therapeutics
Cytoplasmic and Nuclear Receptors
Stromal Cells
Elbow
Articular Range of Motion
Adipocytes
Ankle
Multicenter Studies
Cartilage
Registries
Disease Progression

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Orthopedics and Sports Medicine

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Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors : A study protocol. / Takeuchi, Akihiko; Nomura, Akihiro; Yamamoto, Norio; Hayashi, Katsuhiro; Igarashi, Kentaro; Tandai, Susumu; Kawai, Akira; Matsumine, Akihiko; Miwa, Shinji; Nishida, Yoshihiro; Nakamura, Tomoki; Terauchi, Ryu; Hoshi, Manabu; Kunisada, Toshiyuki; Endo, Makoto; Yoshimura, Kenichi; Murayama, Toshinori; Tsuchiya, Hiroyuki.

In: BMC Musculoskeletal Disorders, Vol. 20, No. 1, 68, 09.02.2019.

Research output: Contribution to journalArticle

Takeuchi, A, Nomura, A, Yamamoto, N, Hayashi, K, Igarashi, K, Tandai, S, Kawai, A, Matsumine, A, Miwa, S, Nishida, Y, Nakamura, T, Terauchi, R, Hoshi, M, Kunisada, T, Endo, M, Yoshimura, K, Murayama, T & Tsuchiya, H 2019, 'Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: A study protocol', BMC Musculoskeletal Disorders, vol. 20, no. 1, 68. https://doi.org/10.1186/s12891-019-2453-z
Takeuchi, Akihiko ; Nomura, Akihiro ; Yamamoto, Norio ; Hayashi, Katsuhiro ; Igarashi, Kentaro ; Tandai, Susumu ; Kawai, Akira ; Matsumine, Akihiko ; Miwa, Shinji ; Nishida, Yoshihiro ; Nakamura, Tomoki ; Terauchi, Ryu ; Hoshi, Manabu ; Kunisada, Toshiyuki ; Endo, Makoto ; Yoshimura, Kenichi ; Murayama, Toshinori ; Tsuchiya, Hiroyuki. / Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors : A study protocol. In: BMC Musculoskeletal Disorders. 2019 ; Vol. 20, No. 1.
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T1 - Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors

T2 - A study protocol

AU - Takeuchi, Akihiko

AU - Nomura, Akihiro

AU - Yamamoto, Norio

AU - Hayashi, Katsuhiro

AU - Igarashi, Kentaro

AU - Tandai, Susumu

AU - Kawai, Akira

AU - Matsumine, Akihiko

AU - Miwa, Shinji

AU - Nishida, Yoshihiro

AU - Nakamura, Tomoki

AU - Terauchi, Ryu

AU - Hoshi, Manabu

AU - Kunisada, Toshiyuki

AU - Endo, Makoto

AU - Yoshimura, Kenichi

AU - Murayama, Toshinori

AU - Tsuchiya, Hiroyuki

PY - 2019/2/9

Y1 - 2019/2/9

N2 - Background: A 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). Methods: This 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. Discussion: This 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 registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000025901) registered on 4/01/2017.

AB - Background: A 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). Methods: This 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. Discussion: This 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 registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000025901) registered on 4/01/2017.

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