Padova

Researchers are evaluating the use of two different surgical techniques for lateral sinus lift procedures in patients who have lost some or all teeth in the upper premolar or molar areas and have severe bone loss in the jaw. The study aims to determine whether the tunnel flap technique is better than the traditional trapezoidal flap technique regarding post-operative symptoms, safety, complication rates, and effectiveness of bone grafting. Participants will undergo the lateral sinus lift surgery using either the tunnel flap technique, which involves a single vertical incision and careful elevation of the flap, or the trapezoidal flap technique, which uses a horizontal incision with two releasing incisions. Both procedures involve creating a trap door in the lateral wall of the maxillary sinus, elevating the sinus membrane, and filling the sinus with a bone graft. Flaps will then be sutured meticulously. After surgery, participants will be contacted by phone the day after the procedure and asked to keep a diary for one week to record pain levels and medication use. Follow-up visits will take place for suture removal and again 30 days later. Dental implants will be placed six months after surgery, followed by prosthetic rehabilitation six months after implant placement. Researchers will monitor the implants for up to 12 months after prosthetic rehabilitation. The main outcome measured is pain and discomfort on the fourth day after surgery using a visual analog scale (VAS).

Researchers are investigating a new treatment approach for metastatic colorectal cancer (mCRC) in patients whose tumors have MGMT silencing and are microsatellite stable (MSS). This approach combines several chemotherapy drugs, including fluoropyrimidines, irinotecan, temozolomide, and bevacizumab, aiming to overcome resistance seen with single chemotherapies. The study includes phase 1b and phase 2 parts, focusing on safety, dosing, and effectiveness of this combination in patients not previously treated for advanced disease. The treatment regimen starts with an induction phase of four 28-day cycles combining 5-fluorouracil, leucovorin, irinotecan, temozolomide, and bevacizumab (FLIRT-bevacizumab), followed by a maintenance phase where 5-FU/LV and bevacizumab are given every two weeks along with oral temozolomide on days 1 to 5 every 28 days. Doses of temozolomide are escalated during treatment to find the recommended phase 2 dose. Bevacizumab, irinotecan, leucovorin, and 5-fluorouracil are administered intravenously every two weeks. Participants undergo tumor assessments before treatment and every eight weeks to monitor disease progression, side effects, and treatment response. The study tracks safety by identifying dose-limiting toxicities during the dose-escalation phase and evaluates the treatment’s efficacy over 24 months. Patients continue treatment until disease progression, unacceptable toxicity, withdrawal, or death. The phase 1b portion has been completed, and the phase 2 part is ongoing.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are studying intismeran autogene combined with pembrolizumab to see if it can stop advanced melanoma, a type of skin cancer that has spread and cannot be removed by surgery, from growing or spreading. This Phase 2 study compares this combination to pembrolizumab with a placebo, aiming to find out if the new treatment helps people live longer without cancer progression. Immunotherapy, which helps the immune system fight cancer, is a standard treatment for advanced melanoma, and intismeran autogene is designed to boost the immune response against a person's specific cancer. Participants receive either intismeran autogene or a placebo through intramuscular injection, along with pembrolizumab given as an intravenous infusion. The study is randomized, double-blind, and controlled, meaning neither participants nor researchers know who gets the active treatment or placebo. This design helps to better understand the effects of intismeran autogene when combined with pembrolizumab. During the study, researchers will monitor participants for up to about 36 months to measure progression-free survival, which means the length of time participants live without the cancer worsening. Assessments include imaging scans to track tumor changes, tumor tissue collection for biomarker analysis, and documentation of any side effects. Participants may also have their mutation status checked and will be observed for safety throughout the study period.

Researchers are evaluating a chemo-free combination of rituximab and golcadomide (CC-99282) as a front-line treatment for older, frail patients newly diagnosed with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). This phase II, multicenter study focuses on patients aged 80 or older who are considered frail based on a simplified geriatric assessment (sGA) and are not eligible for standard anthracycline-based chemotherapy. The study aims to assess the effectiveness of this treatment approach in this vulnerable population. Participants will receive an induction phase of up to six 28-day cycles consisting of golcadomide, rituximab, and dexamethasone only during the first cycle. Response to treatment will be evaluated after four and six cycles to identify patients who are responding. Those achieving at least a partial response will continue as planned, while non-responders will stop protocol treatment and switch to alternative regimens. After induction, involved site radiotherapy is permitted for PET-positive disease. Patients with at least partial response at the end of induction may then enter a consolidation phase with up to six additional 28-day cycles of golcadomide. Interim response checks during consolidation will identify disease progression, leading to treatment discontinuation if needed. Throughout the study, participants will undergo assessments including PET/CT or CT scans to evaluate disease and sarcopenia at baseline and end of treatment. Quality of life will be measured at study entry, during treatment, and follow-up. Follow-up visits will occur every three months for the first year and every six months in the second year, with a total follow-up duration of 24 months. Progression-free survival at 24 months is the primary outcome. Patients with disease progression will be considered treatment failures and followed for survival until study completion.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

The trial investigates the use of volrustomig in participants with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have not shown disease progression after receiving definitive concurrent chemoradiotherapy (cCRT). The study aims to evaluate the efficacy and safety of volrustomig compared to observation in this patient population. Participants have tumors that express PD-L1 and the study is conducted as a Phase III, randomized, open-label, multi-center global trial. Participants are assigned to receive either volrustomig as sequential therapy following cCRT or to an observation group. The treatment period involves monitoring participants who have completed definitive cCRT but remain unresected and have no evidence of metastatic disease. The study focuses on participants with Stage III, IVA, or IVB LA-HNSCC according to AJCC criteria, who have not undergone tumor resection before cCRT and have not been treated with radiotherapy alone. During the study, participants are regularly evaluated for progression-free survival, with follow-up lasting up to approximately 8 years to assess long-term outcomes. Researchers will monitor safety and disease progression closely. The overall participation duration includes screening, treatment or observation, and extended follow-up to capture both efficacy and safety data over time.

This is a long-term follow-up trial to the post-authorisation efficacy and safety (PAES) trial (trial 20-HMedIdeS-19). The trial will include patients who participated in the PAES trial and were transplanted with a new kidney after treatment with imlifidase (trial drug) or standard of care medication. Imlifidase is a medicine used to prevent the body from rejecting a newly transplanted kidney and is used before transplantation in adults who have antibodies against the donor kidney and are considered 'highly sensitised' based on a positive crossmatch test. The purpose of this follow-up trial is to fulfil requirements from the European Medicines Agency (EMA) to continue to evaluate efficacy (kidney function) and safety (side effects) over time, for the patients who were transplanted with a new kidney in the PAES trial. The patients will be followed for up to 5 years after transplantation in the PAES trial to collect valuable long-term data.

Researchers are studying adults with confirmed Primary Biliary Cholangitis (PBC) and cirrhosis, a scarring of the liver caused by damage to bile ducts. PBC is a slowly progressing disease that causes bile acid buildup and further liver damage, which can lead to cirrhosis. This study aims to evaluate if elafibranor, a daily medication, can prevent worsening clinical outcomes such as the need for liver transplant or death, compared to a placebo. It also looks at the safety of long-term elafibranor use and its effect on symptoms like itching and tiredness. Participants will take either an 80 mg tablet of elafibranor or a matching placebo once daily for up to 3.5 years in a double-blind setup, meaning neither the participants nor researchers know who receives which treatment. This long-term treatment period is designed to monitor the drug's impact over time. The study includes two groups: one receiving elafibranor and the other receiving placebo, with treatment lasting up to approximately 42 months. During the study, participants will be regularly assessed from the start until 4 weeks after treatment ends, with a maximum involvement of 3.5 years. Researchers will measure event-free survival, tracking if participants avoid clinical events indicating disease worsening. Safety monitoring will include tracking side effects and overall health, while symptom impact will be evaluated. Participants will provide informed consent and follow the study protocol throughout this extended observation period.