Anal Squamous Cell Carcinoma

The goal of this study is to evaluate the safety and effectiveness of EVOLVE104 in participants with advanced urothelial and squamous cell carcinomas who have previously taken standard treatment options, have declined or have been ineligible for treatment with these medications. Participants with advanced or metastatic cancer who meet all eligibility criteria may be eligible to participate in the study.

The goal of this clinical trial is to see the safety and efficacy of pembrolizumab and lenvatinib in patients with anal squamous cell cancer that cannot be removed through surgery or is spread to other organs. Eligible participants should have also received some form of standard therapy previously for their advanced cancer. Participants will be required to come for a clinic visit and infusion of pembrolizumab. Lenvatinib will be taken by mouth at home based on direction provided by physicians and research team.

The proposed study is a phase II, single arm, open-label trial of MR-guided radiation therapy (RT) with risk stratified RT dose selection in patients with anal cancer. Based on previous data, a risk adaptive treatment approached is proposed in 4 groups: Low risk, standard risk, intermediate risk, and high risk. Human papillomavirus (HPV) DNA will be analyzed to identify novel biomarkers that predict chemoradiotherapy (CRT) response and toxicity.

This is a 20 patient pilot study to examine the feasibility of dose-adapted radiation therapy for the treatment of locally advanced anal squamous cell cancer. The tumor and a patient's anatomy may change during radiation treatment and daily adaption of the radiation plan (i.e., a new daily plan based on the anatomy of the day) may help to maximize the dose to the tumor and minimize the radiation dose to the normal surrounding organs.

Due to the scarcity of data on prognostic and predictive influence on CCA, epidemiological studies evaluating these factors need to be developed in patients with CCA. Therefore, the investigators want to evaluate the profile of patients in the real world and from various parts of the world, describing prognostic factors such as CD4 dosage, time of HIV infection, evaluation of viral load, diagnosis of AIDS, geographic region of diagnosis and treatment, clinical staging, medications concomitant with QRT (risk of drug interactions), comorbidities (possible impact on dose-intensity), use of HAART, time of use of HAART, radiotherapy modality (conventional 3D vs Modulated Beam Intensity \[IMRT\], response to Nigro vs CTII regimens, as well as comparing clinical outcomes with patients without HIV infection.

The majority of anal squamous cell carcinomas (SCC) stem from infection with high-risk human papillomavirus (HPV). Anal SCC is rare among the general population but affects several populations disproportionately. High-risk groups are screened through anal swabs for anal cytology and detection of high risk human papillomavirus (HR HPV). HRA referral is recommended for individuals with abnormal cytology. HRA represents the only method to identify precancerous lesions of the anal canal, with only few specialists knowledgeable about it. At UZ Brussel, the investigators collected a wealth of data about HPV infection and its association with anal pathology. By establishing a comprehensive study, the investigators can delve into this data with specific research questions, conducting valuable research to provide answers to pressing clinical questions and contribute to advancements in medical understanding and treatment.

A single-arm, prospective, Phase II, single-center clinical trial that will investigate if daily online adaptive radiotherapy for anal cancer will significantly reduce early treatment-related GI toxicity compared with the historically reported rate for non-adaptive intensity modulated radiation therapy (IMRT).