Phase I clinical study of oral olaparib in pediatric patients with refractory solid tumors: study protocol

Masatoshi Takagi; Chitose Ogawa; Yuki Aoki-Nogami; Tomoko Iehara; Eri Ishibashi; Minoru Imai; Tetsuro Kihara; Kiyoshi Nobori; Kazuhisa Hasebe; Shuki Mizutani; Toshimi Kimura; Masashi Nagata; Masato Yasuhara; Kenichi Yoshimura; Pariko Yorozu; Hajime Hosoi; Ryuji Koike

doi:10.1186/s12887-019-1409-7

Phase I clinical study of oral olaparib in pediatric patients with refractory solid tumors: study protocol

BMC Pediatr. 2019 Jan 26;19(1):31. doi: 10.1186/s12887-019-1409-7.

Authors

Masatoshi Takagi¹, Chitose Ogawa², Yuki Aoki-Nogami², Tomoko Iehara³, Eri Ishibashi⁴, Minoru Imai⁴, Tetsuro Kihara⁴, Kiyoshi Nobori⁵, Kazuhisa Hasebe⁴, Shuki Mizutani⁴, Toshimi Kimura⁶, Masashi Nagata⁷, Masato Yasuhara⁷, Kenichi Yoshimura⁸, Pariko Yorozu⁵, Hajime Hosoi³, Ryuji Koike⁵

Affiliations

¹ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan. [email protected].
² Department of Pediatric Oncology, National Cancer Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
³ Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
⁴ University Research Administration Division, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁵ Medical Innovation Promotion Center, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁶ Department of Pharmacodynamics, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, 162-8666, Japan.
⁷ Department of Pharmacodynamics, Tokyo Medical and Dental University, Tokyo, Japan.
⁸ Innovative Clinical Research Center, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920-8641, Japan.

Abstract

Background: There is no established standard chemotherapy for recurrent pediatric solid tumors such as neuroblastoma and sarcoma. Since some of these tumor cells show dysfunctions in homologous recombination repair, the goal is to conduct a phase I study of olaparib, a poly(ADP-ribose) polymerase inhibitor. In this clinical trial, the aims are to evaluate the safety, tolerability, and efficacy of olaparib in pediatric patients with refractory solid tumors and to recommend a dose for phase II trials.

Methods: In this open-label, multicenter study, olaparib tablets (62.5, 125, and 187.5 mg/m² b.i.d.) will be administered orally in a standard 3 + 3 dose escalation design. Patients aged 3 to 18 years with recurrent pediatric solid tumors are eligible. Pharmacokinetic and pharmacodynamic analyses will also be performed.

Discussion: This study aims to extend the indications for olaparib by assessing its safety and efficacy in pediatric refractory solid tumor patients.

Trial registration: UMIN-CTR ( UMIN000025521 ); Registered on January 4, 2017.

Keywords: Chemotherapy; Children; Olaparib; Phase I; Poly(ADP-ribose) polymerase; Solid tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Adolescent
Child
Child, Preschool
Clinical Trials, Phase I as Topic* / methods
Humans
Neoplasm Recurrence, Local / drug therapy*
Phthalazines / administration & dosage*
Piperazines / administration & dosage*
Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage*
Research Design*

Substances

Phthalazines
Piperazines
Poly(ADP-ribose) Polymerase Inhibitors
olaparib

Associated data

UMIN-CTR/UMIN000025521