Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer
Abstract This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and there...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-10-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2442 |
| _version_ | 1819032691337592832 |
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| author | Hiroyoshi Suzuki Hiroji Uemura Atsushi Mizokami Narihiko Hayashi Yasuhide Miyoshi Satoshi Nagamori Yutaka Enomoto Hideyuki Akaza Takayuki Asato Tadayuki Kitagawa Kazuhiro Suzuki |
| author_facet | Hiroyoshi Suzuki Hiroji Uemura Atsushi Mizokami Narihiko Hayashi Yasuhide Miyoshi Satoshi Nagamori Yutaka Enomoto Hideyuki Akaza Takayuki Asato Tadayuki Kitagawa Kazuhiro Suzuki |
| author_sort | Hiroyoshi Suzuki |
| collection | DOAJ |
| description | Abstract This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose‐escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose‐limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate‐specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose‐limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK‐385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady‐state Tmax was ~1‐2 hours and mean t1/2z was 67‐79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate‐specific antigen of >90% from baseline were observed through 96 weeks. TAK‐385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. ClinicalTrials.gov: NCT02141659. |
| first_indexed | 2024-12-21T07:05:58Z |
| format | Article |
| id | doaj.art-d73133c273584c7b9fe91120d5bba7e5 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-21T07:05:58Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d73133c273584c7b9fe91120d5bba7e52022-12-21T19:12:07ZengWileyCancer Medicine2045-76342019-10-018135891590210.1002/cam4.2442Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancerHiroyoshi Suzuki0Hiroji Uemura1Atsushi Mizokami2Narihiko Hayashi3Yasuhide Miyoshi4Satoshi Nagamori5Yutaka Enomoto6Hideyuki Akaza7Takayuki Asato8Tadayuki Kitagawa9Kazuhiro Suzuki10Department of Urology Toho University Sakura Medical Center Chiba JapanDepartment of Urology and Renal Transplantation Yokohama City University Medical Center Yokohama JapanDepartment of Integrative Cancer Therapy and Urology Graduate School of Medical Sciences Kanazawa University Kanazawa JapanDepartment of Urology Public University Corporation Yokohama City University Hospital Yokohama JapanDepartment of Urology and Renal Transplantation Yokohama City University Medical Center Yokohama JapanDepartment of Urology Incorporated Administrative Agency National Hospital Organization Hokkaido Cancer Center Sapporo JapanDepartment of Urology Mitsui Memorial Hospital Tokyo JapanDepartment of Strategic Investigation on Comprehensive Cancer Network Interfaculty Initiative in Information Studies/Graduate School of Interdisciplinary Information Studies The University of Tokyo Tokyo JapanOncology Clinical Research Department Oncology Therapeutic Area Unit for Japan and Asia Takeda Pharmaceutical Company Limited Osaka JapanJapan Development Center Takeda Pharmaceutical Company Limited Osaka JapanDepartment of Urology Graduate School of Medicine National University Corporation Gunma University Maebashi JapanAbstract This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose‐escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose‐limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate‐specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose‐limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK‐385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady‐state Tmax was ~1‐2 hours and mean t1/2z was 67‐79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate‐specific antigen of >90% from baseline were observed through 96 weeks. TAK‐385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. ClinicalTrials.gov: NCT02141659.https://doi.org/10.1002/cam4.2442hormone therapyprostate cancer |
| spellingShingle | Hiroyoshi Suzuki Hiroji Uemura Atsushi Mizokami Narihiko Hayashi Yasuhide Miyoshi Satoshi Nagamori Yutaka Enomoto Hideyuki Akaza Takayuki Asato Tadayuki Kitagawa Kazuhiro Suzuki Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer Cancer Medicine hormone therapy prostate cancer |
| title | Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer |
| title_full | Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer |
| title_fullStr | Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer |
| title_full_unstemmed | Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer |
| title_short | Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer |
| title_sort | phase i trial of tak 385 in hormone treatment naive japanese patients with nonmetastatic prostate cancer |
| topic | hormone therapy prostate cancer |
| url | https://doi.org/10.1002/cam4.2442 |
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