Soltech (Belgium)

Metastatic castration-refractory prostate cancer (mCRPC) presents a therapeutic challenge despite advancements in treatment. Once mCRPC is attained, patients face limited survival prospects. Next-line systemic treatment (NEST) is the standard of care for progressive mCRPC, encompassing various therapeutic options with associated toxicity and costs. In patients with oligoprogressive mCRPC, data suggest that progression-directed therapy (PDT), such as metastasectomy or stereotactic body radiotherapy, delays the initiation of NEST. The MEDCARE phase III trial aims to assess the impact of PDT on overall survival (OS) in oligoprogressive mCRPC. In this multicentric, randomised, prospective trial, we aim to randomise 246 patients in 1:1 allocation ratio between the standard-of-care therapy (surveillance or NEST) or PDT while continuing the current systemic treatment. Patients will be stratified based on number of progressive lesions (one vs ≥one), location of progressive lesions (local recurrence, N or M1a vs M1b or M1c) and previous systemic therapy (palliative androgen-deprivation therapy [pADT] vs pADT + androgen receptor-targeted agent or patients who received docetaxel in the past). The primary endpoint is OS, and the secondary endpoints include quality of life, radiographic progression-free survival (PFS), modified PFS, prostate cancer-specific survival and PDT-induced toxicity. This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint.

BackgroundPatients diagnosed with metastatic castration-refractory prostate cancer (mCRPC) rely on a limited number of therapeutic agents resulting in a median survival of 2–3 years. A subgroup of those patients with mCRPC presents with oligoprogressive disease, with a limited number of progressive lesions while other metastases are still controlled by ongoing systemic treatment.MethodsIn this single arm prospective phase II trial, we aim to include 18 patients with oligoprogressive mCRPC (1–3 metastases and/or local recurrence) who will be treated with metastasis-directed therapy to all visible progressive lesions. Progression is based on conventional imaging, as the use of PSMA PET-CT is considered investigational. However all patients will undergo PSMA PET-CT and the images will be blinded until progression. Primary endpoint is the postponement of the start of next-line systemic treatment (NEST) and the additional clinical value of PSMA PET-CT. Recruitment of patients for this trial started in January 2020 and will be completed approximately by December 2020.DiscussionIn this phase 2 trial on oligoprogressive mCRPC, we will investigate the benefit of progression-directed therapy while continuing ongoing systemic treatment. We hypothesize that progression-directed therapy (PDT) with surgery or stereotactic body radiation therapy for these oligoprogressive lesions will postpone the start of next-line systemic treatment and therefore serve as a new or add-on therapy in the spectrum of treatments available for mCRPC. The results of this trial will serve as guidance for a later randomized phase 3 trial. All participants are given an information sheet and are required to give written informed consent. Results will be published in a peer-reviewed journal.Trial registrationThis study is registered at ClinicalTrials.gov: NCT04222634 (December 18th 2019).

In this paper, we investigate the operating principle and the injection efficiency of the punch-through-assisted hot hole injection mechanism for programming nonvolatile memory cells by means of full-band Monte Carlo transport simulations of realistic device structures. The effects of terminal bias and cell scaling on the injection efficiency and the uniformity of charge injection along the channel are analyzed in detail.