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Clinical Trial
. 2018 May 25;18(1):596.
doi: 10.1186/s12885-018-4453-z.

A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer

Yoshiki Hirooka  1 , Hideki Kasuya  2 , Takuya Ishikawa  3 , Hiroki Kawashima  3 , Eizaburo Ohno  3 , Itzel B Villalobos  2 , Yoshinori Naoe  2 , Toru Ichinose  2 , Nobuto Koyama  4 , Maki Tanaka  4 , Yasuhiro Kodera  5 , Hidemi Goto  3
Affiliations
Clinical Trial

A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer

Yoshiki Hirooka et al. BMC Cancer. .

Abstract

Background: Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study.

Methods: This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment.

Results: Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR).

Conclusions: HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies.

Trial registration: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.

Keywords: EUS-guidance; HF10; Oncolytic virus; Pancreatic cancer.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethical Committee of Nagoya University Hospital (Reference number: 3299). Written informed consents to participate were obtained from all the patients in this study.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Schedule of the treatment
Fig. 2
Fig. 2
a A cut surface of the pancreatic body showed a fibrotic tissue in the area where the tumor was located (HF-1-05). b On histological analysis, 99% of the cancer cells had disappeared and had been replaced with fibrotic tissue. c High-power photomicrograph revealed a minute residual cancer tissue (circle)
Fig. 3
Fig. 3
Evaluation of CD4+ and CD8+ cells infiltration around the cancer tissue (HF-1-05). a Three areas in different distances (circle) from the residual cancer (dot-line circle) were evaluated. b, c Infiltration of CD4+ and CD8+ cells was significant in the fibrosis near the residual cancer tissue (area 3) and it became obscure as the areas receded from the cancer tissue
Fig. 4
Fig. 4
a A cut surface of the pancreatic head of HF-2-02. The left image showed showed fibrosis in the middle and the right showed a magnified image. b Histopathological findings of the tumor in the pancreatic head showed 90% disappearance of cancer cells with fibrosis
Fig. 5
Fig. 5
Evaluation of CD4+ and CD8+ cells infiltration around the cancer tissue (HF-2-02). a Three different areas (circle) were evaluated. b, c High-power photomicrograph showed diffuse persistence of cancer cells (arrow), and infiltration of CD8+ cells was detected along by the cancer cells
See this image and copyright information in PMC

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References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi: 10.3322/caac.21332. - DOI - PubMed
    1. Furuse J, Gemma A, Ichikawa W, Okusaka T, Seki A, Ishii T. Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis. Jpn J Clin Oncol. 2017;47(9):1–8. doi: 10.1093/jjco/hyx075. - DOI - PMC - PubMed
    1. Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999;189(1):1–7. doi: 10.1016/S1072-7515(99)00075-7. - DOI - PubMed
    1. Myrehaug S, Sahgal A, Russo SM, Lo SS, Rosati LM, Mayr NA, Lock M, Small W, Jr, Dorth JA, Ellis RJ, et al. Stereotactic body radiotherapy for pancreatic cancer: recent progress and future directions. Expert Rev Anticancer Ther. 2016;16(5):523–530. doi: 10.1586/14737140.2016.1168698. - DOI - PubMed
    1. Eissa IR, Naoe Y, Bustos-Villalobos I, Ichinose T, Tanaka M, Zhiwen W, Mukoyama N, Morimoto T, Miyajima N, Hitoki H, et al. Genomic signature of the natural oncolytic herpes simplex virus HF10 and its therapeutic role in preclinical and clinical trials. Front Oncol. 2017;7:149. doi: 10.3389/fonc.2017.00149. - DOI - PMC - PubMed

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