Takahashi Kenta, Ishibashi Eri, Kubo Toshio, Harada Yohei, Hayashi Hideyuki, Kano Masayuki, Shimizu Yasushi, Shirota Hidekazu, Mori Yukiko, Muto Manabu, Ishioka Chikashi, Dosaka-Akita Hirotoshi, Matsubara Hisahiro, Nishihara Hiroshi, Sueoka-Aragane Naoko, Toyooka Shinichi, Hirakawa Akihiro, Tateishi Ukihide, Miyake Satoshi, Ikeda Sadakatsu
Center for Innovative Cancer Treatment.
Medical Innovation Promotion Center, Tokyo Medical and Dental University, Tokyo.
Medicine (Baltimore). 2020 Aug 7;99(32):e21457. doi: 10.1097/MD.0000000000021457.
Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol.
METHODS/DESIGN: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response.
The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab.
This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150.
人表皮生长因子受体2（HER2）基因扩增和突变已成为致癌驱动因素和治疗靶点，不仅限于乳腺癌和胃癌，还存在于多种癌症中。然而，即便发现了可采取行动的基因改变，这些癌症中HER2扩增的发生率仍低于5%。在如此罕见的病例中开展传统的随机对照试验难度太大。因此，我们设计了一项不区分器官的篮子研究，在一个研究方案中涵盖了多种存在HER2扩增的实体癌。
方法/设计：本试验是在日本开展的一项多中心、单臂、篮子2期研究。符合条件的患者为存在HER2扩增且标准治疗后病情进展的实体癌患者，或尚无标准治疗方案的罕见癌症患者。目标癌症包括胆管癌、尿路上皮癌、子宫癌、卵巢癌以及其他通过下一代测序技术进行综合基因组分析检测到HER2扩增的实体癌。总共38例患者将接受曲妥珠单抗和帕妥珠单抗联合治疗，每3周一次，直至疾病进展、出现无法耐受的毒性反应、死亡或患者拒绝治疗。主要终点是客观缓解率，次要终点是无进展生存期、总生存期和缓解持续时间。
本试验的目的是评估曲妥珠单抗和帕妥珠单抗联合治疗对局部晚期或转移性、存在HER2扩增的实体癌患者的安全性和疗效。我们的试验设计并非聚焦于某一种器官类型，而是采用了一项聚焦于HER2扩增的篮子研究，无论癌症的部位或起源如何。我们的研究结果将推进关于使用曲妥珠单抗和帕妥珠单抗联合治疗局部晚期、罕见的存在HER2扩增的实体癌的临床和科学认知。
本试验于2019年2月25日在日本临床试验注册中心（jCRT）注册，注册号为jRCT2031180150。
