scholarly journals A Phase 2, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases

2021 ◽  
Author(s):  
Nobuaki Matsubara ◽  
Hirotsugu Uemura ◽  
Satoshi Nagamori ◽  
Hiroyoshi Suzuki ◽  
Hiroji Uemura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant

A phase II, open-label, multi-arm study of TAS-115 for castration-resistant prostate cancer patients with bone metastases.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 164-164
Author(s):  
Hiroji Uemura ◽  
Nobuaki Matsubara ◽  
Hirotsugu Uemura ◽  
Satoshi Nagamori ◽  
Hiroyoshi Suzuki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Bone Scan ◽  
Response Rate ◽  
Short Form ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Anti Tumor Activity

164 Background: TAS-115, a novel multi-kinase (eg, MET, VEGFR) inhibitor has also shown to inhibits Feline McDonough Sarcoma oncogene (FMS) kinase, Anti-tumor activity against bone metastases was observed in the preclinical and phase1 study. In this phase 2 study, the efficacy and safety of TAS-115 were evaluated in castration-resistant prostate cancer (CRPC) patients (pts) with bone metastases. Methods: This was a phase 2, open-label, multi-arm study for CRPC pts with bone metastases to evaluate the clinical anti-tumor activity of TAS-115. Pts who had visceral metastases were ineligible for this study. TAS-115 was given orally, once daily, and schedule of 5 days on/2 days off each week was repeated. This study had 2 cohorts (A and B). In cohort A, TAS-115 ranging from 200 to 400 mg/day with abiraterone acetate was given to pts prior to docetaxel. In cohort B, CRPC pts who had symptomatic bone metastases, post or unfit to docetaxel, were randomized in a 1:1 to 400 or 600 mg/day of TAS-115. The primary endpoint was bone scan index (BSI) response rate at week 12, defined as ≥ 30% decrease of BSI from baseline. BSI is a quantitative assessment of bone scan data calculated by software (BONE NAVI). Results: From Nov 2016 to Jul 2018, a total of 50 pts received TAS-115 (24 pts in cohort A and 26 pts in cohort B). BSI response rate at week 12 and best BSI response was 20.8 % and 37.5% in cohort A, and 15.4 % and 19.2% in cohort B, respectively. Any reduction of BSI was observed in 70.8% of cohort A and 61.5% of cohort B. In cohort B, pain was assessed using the Brief Pain Inventory short form and improvement was observed in 61.5% of pts. Furthermore, the reduction of bone-turnover marker (BAP, P1NP, NTx and TRACP-5b) were observed in both cohorts, but not PSA response. The major (≥ 10%) Grade 3/4 treatment-related adverse drug reactions were hypophosphataemia (21%) in cohort A, and anemia (23%), hypophosphataemia (12%) and neutrophil count decreased (12%) in cohort B. Conclusions: Preliminary anti-tumor activity to bone lesion and improved pain were observed in CRPC pts with bone metastases, and safety of TAS-115 was acceptable. TAS-115 could be a novel therapeutic agent with a favorable safety profile for CRPC with bone metastases. Clinical trial information: JapicCTI-163448.

A phase I/II study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): A trial in progress.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS182-TPS182
Author(s):  
Justin Shaya ◽  
Wanling Xie ◽  
Biren Saraiya ◽  
Mamta Parikh ◽  
Edmund Folefac ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastases ◽  
Phase 1 ◽  
Parp Inhibitors ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223

TPS182 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-stranded breaks leading to cell death and has demonstrated improvement in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. PARP inhibitors, including olaparib and rucaparib, inhibit repair of DNA single-stranded beaks and have demonstrated clinical efficacy in mCRPC patients harboring alterations in the homologous recombination repair (HRR) pathway. In extensive preclinical cancer models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the clinical hypothesis that the combination of radium-223 with olaparib will demonstrate anti-tumor activity in patients with mCRPC irrespective of underlying HRR deficiency status. Methods: This is an open label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of olaparib in combination with radium-223 in men with mCRPC with bone metastases. Patient must have 2 or more bone metastases and at least 1 bone metastasis that has not been treated with prior radiation therapy. Key exclusion criteria include the presence of visceral metastases or malignant lymphadenopathy exceeding 4 cm and prior therapy with radium-223 and/or PARP inhibitors. The phase 1 component of the study uses a 3+3 dose escalation design to determine the recommended phase 2 dose of olaparib in combination with standard of care dosing of Radium-223. The primary endpoint of the phase 1 component is safety. The phase 2 component of the study is an open-label, randomized study evaluating the combination of olaparib and radium-223 compared to radium-223 alone. The primary endpoint of the phase 2 component is radiographic progression-free survival as defined by Prostate Cancer Working Group 3 guidelines for bone metastases and RECIST v1.1 for non-bone metastases. Secondary endpoints include time to PSA progression, PSA response, time to subsequent therapy, time to first skeletal event, overall survival, and safety. Exploratory endpoints include stratification of response based on HRR alterations, whole exome sequencing of plasma cell free DNA both at baseline, on treatment, and at progression, and evaluation of changes in the tumor immune microenvironment with therapy. As of October 1, 2020, the phase 1 component has completed accrual and we anticipate opening the phase 2 component by December 2020. Clinical trial information: NCT03317392.

scholarly journals Re‐treatment with radium‐223: 2‐year follow‐up from an international, open‐label, phase 1/2 study in patients with castration‐resistant prostate cancer and bone metastases

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1683-1691 ◽  
Author(s):  
Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
Maria José Méndez Vidal ◽  
Daniel Keizman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223 ◽  
Open Label Phase

scholarly journals Impact of pegfilgrastim as primary prophylaxis for metastatic castration-resistant prostate cancer patients undergoing cabazitaxel treatment: an open-label study in Japan

2019 ◽  
Vol 49 (8) ◽  
pp. 766-771 ◽  
Author(s):  
Takeo Kosaka ◽  
Hiroji Uemura ◽  
Makoto Sumitomo ◽  
Kenichi Harada ◽  
Mikio Sugimoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Primary Prophylaxis ◽  
Granulocyte Colony Stimulating Factor ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Effective Treatment Option ◽  
Open Label Study ◽  
Castration Resistant ◽  
Stimulating Factor

Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduced incidence of febrile neutropenia in Japanese metastatic castration-resistant prostate cancer patients. Cabazitaxel+G-CSF therapy was a safe and effective treatment option.

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