Genolier

Researchers are evaluating whether combining pelabresib with ruxolitinib improves clinical outcomes compared to ruxolitinib alone in adults with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis who have not previously received Janus kinase inhibitor therapy. This phase 3 study includes participants classified as intermediate-1, intermediate-2, or high-risk by the Dynamic International Prognostic Scoring System (DIPSS). The trial aims to assess spleen response and symptom changes over time. The trial consists of several periods: a screening phase up to 28 days before starting treatment to confirm eligibility and perform baseline assessments; a treatment phase with 21-day cycles where participants receive pelabresib or placebo for 14 days plus continuous ruxolitinib; a safety follow-up for 30 days after treatment ends; an efficacy follow-up every 12 weeks for those without disease progression; and a survival follow-up every 12 weeks for participants with disease progression or new therapy. Pelabresib is given as tablets, and ruxolitinib is administered continuously throughout treatment. Participants undergo regular site visits and assessments including spleen imaging, laboratory tests, bone marrow biopsies, and symptom questionnaires. Researchers monitor spleen volume reduction and changes in total symptom score at 24 weeks as primary outcomes. Safety is tracked during and after treatment, with long-term follow-up to gather survival data and ongoing disease status. The study continues until disease progression, unacceptable toxicity, withdrawal, or other protocol-defined reasons.

Researchers are evaluating treatments for patients with clinically node positive breast cancer who undergo upfront surgery. The study aims to compare tailored axillary surgery (TAS) combined with axillary radiotherapy (ART) against the standard axillary lymph node dissection (ALND) to see which approach results in better arm-related quality of life and fewer cases of lymphedema two years after treatment. This trial addresses the concern that ALND, while standard, can cause significant harm and morbidity, and seeks to determine if TAS plus ART can reduce this burden. Participants are randomly assigned to receive either ALND, which involves surgical removal of lymphatic tissue in the armpit area, or the combination of TAS and ART. TAS targets positive lymph nodes more selectively than ALND and removes fewer nodes, while ART involves radiation treatment to the axillary region. The trial is conducted in the upfront surgery setting, with prior clipping of the most suspicious axillary lymph node to aid in treatment precision. During the study, participants will complete quality of life questionnaires and be closely monitored for the development of lymphedema over two years following randomization. The main outcomes measured are changes in arm-related quality of life and the occurrence of lymphedema. Safety and treatment effects will be tracked through regular follow-up visits, with the overall goal of improving patient well-being and reducing treatment-related side effects.

Researchers are evaluating the use of vacuum-assisted biopsy (VAB) as a less invasive method to detect residual tumor tissue in breast cancer patients who have undergone neoadjuvant chemotherapy (NAC). NAC is commonly used to shrink tumors before surgery and can lead to complete pathologic remission in over half of aggressive breast cancer types. However, current imaging methods like ultrasound, mammography, and MRI are not reliable enough to confirm if the tumor has been fully eliminated, so surgery remains necessary to assess or remove any remaining disease. In this trial, patients who show a radiological complete or near-complete response after NAC will undergo VAB guided by ultrasound or mammography immediately before their scheduled breast surgery. This biopsy procedure aims to collect tissue samples from the former tumor site to better detect any residual cancer cells. The accuracy of this biopsy will then be compared to the standard surgical tissue analysis to evaluate if VAB can serve as a reliable pre- or intra-operative tool. Participants will be involved in diagnostic imaging and biopsy procedures shortly before their routine breast surgery. Researchers will assess the sensitivity of the VAB in detecting residual tumor tissue within six weeks after patient registration. The study includes monitoring of biopsy results against surgical pathology findings to determine VAB's diagnostic value. Participants must meet specific eligibility criteria and will be followed closely during the trial to ensure safety and accurate data collection.

Researchers are evaluating the use of doxycycline to target cancer stem cells in patients with early stage estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. These cancer stem cells are thought to cause treatment resistance, tumor relapse, and spread. The study aims to see if adding doxycycline to neoadjuvant chemotherapy improves treatment response by reducing these resistant cells, measured by changes in a stemness marker called ALDH1 and the rate of complete pathological response after surgery. This is a phase II, single-arm, open-label trial investigating these effects in ER+/HER2- breast cancers. Participants will receive neoadjuvant chemotherapy consisting of 4 cycles of epirubicin and cyclophosphamide followed by 12 weekly doses of paclitaxel (or nab-paclitaxel). Doxycycline, an antibiotic thought to target cancer stem cells, will be given alongside this chemotherapy. Following chemotherapy, patients will undergo standard curative surgery. Tumor samples will be collected before treatment and after surgery if residual tumor remains to analyze the effects of doxycycline on cancer stem cells and tumor characteristics. During the study, patients will be monitored from registration until 30 days after their last treatment dose. Assessments will include evaluating the proportion of tumors positive for ALDH1 before and after therapy and determining the pathologic complete response rate—defined as no invasive cancer remaining in the breast or lymph nodes. Additional translational research will explore tumor biology using biopsies and organoid cultures. Safety, treatment adherence, and patient outcomes will be carefully followed throughout the trial.