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Addition of bevacizumab and paclitaxel as induction therapy prior to standard atezolizumab and nab-paclitaxel in patients with programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) may help to overcome vascular endothelial growth factor-associated resistance mechanisms that limit the immune-mediated antitumour efficacy of atezolizumab and nab-paclitaxel.
The Induction Therapy of PTX+BV Followed by Atezolizumab+Nab-PTX for PD-L1+TNBC (INDUCE) study is a multicentre, randomised, open-label, phase II trial designed to evaluate the efficacy and safety of two cycles of induction therapy with bevacizumab and paclitaxel followed by atezolizumab and nab-paclitaxel compared with standard atezolizumab and nab-paclitaxel in patients with PD-L1-positive mTNBC. The primary outcome of the study is progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumours, V.1.1. We have estimated that 89 PFS events are needed to allow a power of 80% to detect a difference between treatment groups at a one-sided significance level of 10% in this study. The target sample size is set to 106 patients to account for dropouts.
The study protocol and informed consent form have been approved by the Certified Research Review Board at the Nagoya University Graduate School of Medicine, Nagoya, Japan. Study results will be presented at international conferences and published in a peer-reviewed journal.
jRCTs041240039 NCT06793553.
by Gen Tsujio, Masakazu Yashiro, Yuichiro Miki, Kohei Matsuoka, Koji Maruo, Mami Yoshii, Tatsuro Tamura, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Shigeru Lee, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Masaichi Ohira, Kiyoshi Maeda
BackgroundOur group revealed that the combination of intra-operative stamp cytology and peritoneal lavage cytology (CY) improved the identification of individuals with high risk of peritoneal metastasis. In this exploratory Phase II study, we aimed to evaluate the effect on relapse-free survival (RFS) of extensive intraoperative peritoneal lavage (EIPL) for gastric cancer with positive peritoneal cytology (CY1) and/or stamp cytology positive (stamp+).
Materials and methodsThis study was a single arm, multi-institutional, exploratory phase 2 trial to assess the effects of EIPL after open gastrectomy for gastric cancer with CY1 and/ or stamp+. The primary endpoint was RFS. Secondary endpoints were overall survival (OS), postoperative recurrence site and incidence of postoperative adverse events.
ResultsBetween 2017 and 2021, 13 patients from 2 institutions were enrolled in this study. Because of the recent decline in open abdominal surgery, the number of cases did not increase and the trial was closed due to lack of applicants at 13 cases. Median 3-year RFS was 14.5 months (95% CI 5.4-NA), median 3-year OS was not reached (95% CI 14.5-NA) and median3-year peritoneal RFS was 16.0 months (95% CI 5.4-NA). Median 3-year peritoneal RFS rate was 83% in CY0 and stamp+ cases (n=6), and 0% in CY1 and stamp+/- cases (n=7). (Log-rank p=0.015).
ConclusionBecause of the slow accrual pace and early stop of the trial, we were not able to evaluate the prespecified endpoints thoroughly. However, EIPL might be effective to prevent perineal recurrence, especially in CY0 and stamp+ case.
The standard treatment for unresectable head and neck cancer typically involves radiotherapy (RT) alone or chemoradiotherapy (chemo-RT). Non-squamous cell carcinomas exhibit relatively low radiosensitivity, limiting the efficacy of conventional photon RT. Carbon-ion (C-ion) RT, characterised by high linear energy transfer (LET) and high relative biological effectiveness (RBE), has shown promising outcomes in treating radioresistant head and neck cancers. However, local recurrences still occur, and further improvements in treatment outcomes are needed. To enhance the local control rate, an increase in dose-averaged LET (LETd) to the tumour was considered.
Following a simulation study, a clinical trial was conducted to optimise LETd using only C-ion therapy, and its safety was confirmed. However, in this clinical trial, LETd could only be increased to approximately 70 keV/μm. To further escalate LETd, multi-ion therapy using ions heavier than carbon was developed. Simulation studies demonstrated that multi-ion therapy incorporating carbon, oxygen and neon ions could increase LETd up to 90 keV/μm, regardless of tumour size, while maintaining high-dose uniformity within the tumour. Based on these results, a clinical study was planned to evaluate the safety of escalating LETd from 70 keV/μm to 90 keV/μm using multi-ion therapy. The primary objective of this study is to evaluate the safety of escalating LETd to the tumour using multi-ion therapy for head and neck cancer, with the secondary goal of identifying the maximum tolerated LETd.
This is a non-randomised, open-label, phase 1 study focused on LETd escalation. A maximum of 18 patients with histologically confirmed inoperable head and neck malignancies will be enrolled. All patients will receive multi-ion therapy using helium, carbon, oxygen or neon ions, either alone or in combination, at an RBE-weighted dose ranging from 57.6 to 70.4 Gy, delivered in 16 fractions (4 fractions per week) over 4 weeks. The specific dose will be determined according to histology. LETd escalation will begin at 70 keV/μm and will increase by 10 keV/μm increments, reaching a maximum of 90 keV/μm. The safety of multi-ion therapy will be assessed based on the frequency and severity of dose-limiting toxicities, monitored up to 90 days after the initial irradiation. Patients will be followed up according to the protocol for 180 days after the initial multi-ion therapy irradiation.
The study protocol has been approved by the National Institutes for Quantum Science and Technology Certified Review Board (#L24-002). The results will be published in a peer-reviewed journal and presented at a scientific conference.
jRCTs032240451.
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