Chemotherapy

The main goal of this study is to investigate the effectiveness and safety of chemotherapy agents in the treatment of participants with BPDCN and to provide comparator arm data to the prospective ELZONRIS registry study (STML-401-0521).

The purpose of this study is to learn more about a new medicine called PF-08634404, and how well it works in people with cancer of the colon or rectum (CRC)). The goal is to understand if the new study medicine, combined with chemotherapy that is approved for colorectal cancer, can help people whose cancer has spread or returned after treatments taken before. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have colorectal cancer that has spread to other parts of your body. * Be in good enough health to receive study treatment. * Should not be pregnant before starting treatment. Participants will be randomized (like flipping a coin) to one of 2 different treatment arms. The first arm (Arm A) will include the new medicine PF-08634404 in combination with chemotherapy that is approved for colorectal cancer, and the second arm (Arm B) will include an approved medicine for colorectal cancer, called Bevacizumab, in combination with chemotherapy that is approved for this type of cancer. Participants and their doctors will not know which arm they are being assigned to. Participants will receive all the study medications through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, and participants may continue receiving it if it is helping and they are not experiencing serious side effects. The medicine will be given at a clinical site, where trained medical staff will check participants during and after each treatment. * The study is expected to last approximately 33 months for each participant. * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will return for a final visit about 30 to37 days later to check their health and review any side effects. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records to check on health status and any new treatments.

This clinical trial is designed to assess the efficacy and safety of the triplet combination of trastuzumab deruxtecan (ENHERTU, T-DXd, DS-8201a) plus a fluoropyrimidine plus pembrolizumab versus standard of care (SoC) chemotherapy plus trastuzumab plus pembrolizumab as first-line therapy in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS ≥1 gastric or GEJ cancer in the Main Cohort. An Exploratory Cohort will also be evaluated to assess the efficacy and safety of T-DXd plus a fluoropyrimidine versus SoC chemotherapy plus trastuzumab in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS \<1 gastric or GEJ cancer.

This study was originally opened on 10/22/2024 as an open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) to receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. As of 7/20/2026, the study was amended to a single arm receiving neoadjuvant chemotherapy, cemiplimab every 3 weeks for 3 cycles and alirocumab every 4 weeks prior to surgery. The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.

This phase II trial tests the impact of biomarkers in predicting initial treatment (first-line) PD1 or PD-L1 (PD\[L\]-1)-based immunotherapy response and in selecting second-line treatment in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). Response and survival rates in advanced stage NSCLC, unlike other cancers, rely on response to first-line therapy. Immunotherapy with PD(L)1-based therapy, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. While immunotherapy has improved survival rate, the prognosis remains poor with most patients receiving chemotherapy after immunotherapy. Many types of tumors tend to lose cells or release different types of cellular products including their deoxyribonucleic acid (DNA) which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. The first part of this trial, studying samples of blood and tissue in the laboratory from patients receiving immunotherapy may help doctors learn more about the effects PD(L)1-based therapy on cells. It may also help doctors understand how well patients respond to treatment and may help develop new individualized treatment strategies. The second part of this trial also tests the effect of second-line immunotherapy, such as tremelimumab and durvalumab or adagrasib and bevacizumab, in treating patients with NSCLC with specific genetic mutations that is growing, spreading or getting worse (progressive). Tremelimumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adagrasib, a type of targeted therapy, may stop the growth of tumor cells by blocking a protein needed for tumor cell growth and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving second-line immunotherapy, tremelimumab and durvalumab or adagrasib with bevacizumab, may be safe, tolerable, and/or effective in treating patients with stage IIIB/IV NSCLC with specific genetic mutations.

This study is evaluating two treatment approaches for patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) who have a good response to 2-3 cycles of induction chemoimmunotherapy. Patients who achieve either a clinical complete response (cCR) or partial response (PR) will be eligible to join the study. After enrollment, patients will choose, together with their doctors, between surgery and definitive chemoradiotherapy (dCRT). Patients in the surgery group will undergo esophagectomy with lymph-node dissection. Patients in the dCRT group will receive radiotherapy together with chemotherapy. After surgery or dCRT, all patients will receive camrelizumab immunotherapy for up to 12 months if they have recovered sufficiently and have no evidence of disease progression. The study will compare the effectiveness and safety of these two treatment approaches and will assess whether dCRT can provide an organ-preserving treatment option for selected patients. The study will enroll approximately 120 patients.

This phase II trial studies how well chemotherapy with or without radiation or surgery works in treating participants with esophageal or gastric cancer that has spread to less than 3 places in the body (oligometastatic). Drugs used in chemotherapy, such as fluorouracil and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Surgery, such as complete surgical resection, may stop the spread of tumor cells by surgically removing organs or tumors. Giving chemotherapy with radiation or surgery may work better than chemotherapy alone in treating participants with oligometastatic esophageal or gastric cancer.

Esophageal cancer (EC) ranks among the leading malignant gastrointestinal tumors globally in terms of both incidence and mortality. Cases of EC in China account for over 50% of the global total, with squamous cell carcinoma being the primary pathological type. Locally advanced EC (LAEC), particularly cases where radical surgical resection is not feasible, exhibits high recurrence rates and low 5-year survival rates. However, studies have shown that patients with LAEC who undergo comprehensive treatment followed by surgery experience significantly prolonged survival and improved quality of life compared to those who do not receive surgical intervention. Current conversion treatment regimens under investigation include: chemotherapy alone, chemoradiotherapy, immunotherapy combined with chemotherapy, and immunotherapy combined with chemoradiotherapy-each of these approaches has distinct advantages and limitations. Immunochemotherapy has emerged as a current research focus: it not only demonstrates significantly superior efficacy compared to chemotherapy alone but also exhibits lower cumulative toxicity than radiotherapy-combined conversion regimens, resulting in a more favorable overall benefit-risk ratio. As such, it represents the most promising conversion treatment strategy. Retrospective and prospective clinical studies have shown that low-dose radiotherapy targeting the small intestine can enhance the anti-tumor response of immune checkpoint inhibitors (ICIs) in patients with advanced solid tumor, prolong their overall survival, and increase the incidence of the abscopal effect. Further mechanistic investigations have revealed that intestinal low-dose radiotherapy (ILDR) may augment the immune cancerous lethality by modulating the gut microbiota and their metabolic profiles. Based on the findings from these preliminary studies, the current research plans to conduct a prospective phase II single-arm clinical trial to investigate the efficacy and safety of ILDR combined with immunochemotherapy as conversion therapy in patients with borderline resectable or unresectable esophageal squamous cell carcinoma (BR/UR ESCC). This research plans to enroll at least 39 evaluable cases or a total of 39 cases in two seperated stages, focusing on patients with thoracic BR/UR ESCC. Patients will receive a single fraction of ILDR with a mean dose of 1 Gy, concurrently with 3 cycles of albumin-bound paclitaxel (260 mg/m² on day 1), cisplatin (75 mg/m² on day 1), and tislelizumab (200 mg on day 1). The efficacy and safety of the treatment will be evaluated throughout the study.

This prospective, non-randomized, concurrent parallel-controlled study will evaluate treatment response and resistance mechanisms in patients with pancreatic neuroendocrine tumors with liver metastases (pNET-LM) receiving second-line systemic therapy after failure of first-line treatment. Eligible patients will receive either lenvatinib combined with chemotherapy or chemotherapy alone according to the study protocol and clinical treatment strategy. The clinical efficacy and safety of the two treatment strategies will be evaluated using objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Peripheral blood samples will be collected before treatment, during early treatment, and at disease progression. Circulating cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMCs) will be analyzed to investigate molecular and immune changes associated with treatment response, primary resistance, and acquired resistance. The study aims to identify potential biomarkers for predicting treatment response and to improve understanding of resistance mechanisms in pNET-LM.

The goal of this clinical trial is to learn if histotripsy plus chemotherapy works to treat unresectable, bilobar liver- confined colorectal cancer liver metastasis (CRLM). The main question this clinical trial aims to answer is: • Does the management of this condition with uninterrupted palliative chemotherapy and histotripsy demonstrate improved progression-free survival? Participants will: * Receive chemotherapy treatment per standard procedure. * Undergo histotripsy treatment according to current standard procedures at Cleveland Clinic. * Occasionally receive Computerized Tomography (CT) scan with and without contrast, give biopsy of treated and untreated liver lesions, and participate in a blood draw of up to 3 teaspoons at each in-person visit. * Participate in genetic testing, as a part of the standard of care for the treatment.

This phase III trial compares minimally invasive surgery (MIS) to laparotomy in treating patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who are receiving chemotherapy before and after surgery (neoadjuvant chemotherapy). MIS is a surgical procedure that uses small incision(s) and is intended to produce minimal blood loss and pain for the patient. Laparotomy is a surgical procedure which allows the doctors to remove some or all of the tumor and check if the disease has spread to other organs in the body. MIS may work the same or better than standard laparotomy after chemotherapy in prolonging the return of the disease and/or improving quality of life after surgery.

Purpose of the Study: This clinical study investigates whether a shorter or longer duration of systemic therapy before local treatment (surgery or radiation) results in better disease control in patients with esophageal or gastric cancer with a limited number of metastases, also known as oligometastases. Background: In about 25% of patients with advanced esophageal or gastric cancer, the disease spreads to only a few sites (oligometastatic disease). Prior studies suggest that local treatment after systemic therapy may extend survival in this subgroup. However, it is unclear how long systemic therapy should last before initiating local treatment. The OMEC-5 study aims to clarify this. Study Design: Initiated by Amsterdam UMC and UMCU and conducted in multiple hospitals across Europe. Total of 414 patients to be enrolled. Duration: \~53 months (35 months enrollment + 18 months follow-up). Approved by the medical ethics committee at Amsterdam UMC. Procedure: Eligibility screening: Includes physical exam, blood tests (incl. circulating tumor cells), medical history review, and confirmation of oligometastases by an expert panel. Initial treatment: All participants receive 4 months of standard systemic therapy (chemotherapy + immunotherapy and/or targeted therapy depending on tumor markers like HER2 or Claudin 18.2). Response assessment (Review 1): Imaging and/or laparoscopic examination. If oligometastases persist and tumors have not progressed, participants are randomized into two groups: Group A (longer systemic therapy): 4 more months of systemic therapy, then local treatment if disease is stable, followed by 4 months of immunotherapy ± targeted therapy. Group B (shorter systemic therapy): Immediate local treatment followed by 4 months of systemic therapy, then reassessment and potentially 4 months of immunotherapy ± targeted therapy. Follow-up: Regular scans and quality-of-life questionnaires (5 times), and periodic blood sampling (4 times). Treatments Involved: Chemotherapy: CapOx or FOLFOX Immunotherapy: nivolumab or pembrolizumab Targeted therapy: trastuzumab (HER2-positive) or zolbetuximab (Claudin 18.2-positive) Potential Benefits and Risks: Patients may benefit from better disease control and a personalized treatment strategy. Known side effects relate to the standard treatments used (chemo, immuno, targeted therapies), and no extra medical risk is expected beyond routine care. Possible inconveniences include blood draws, scans, minor surgery (laparoscopy), and time investment. Data and Sample Handling: Personal data and tumor/blood samples for exploratory research (if patients consent) are coded and securely stored. Data may be used for future cancer research if the patient consents. Participants can withdraw at any time. Confidentiality and Privacy: Patient data are kept confidential, and participants have rights to access or delete their data. Privacy measures comply with GDPR and Dutch law. Compensation and Insurance: Participation is voluntary, with no financial compensation. Standard treatment costs are covered by healthcare insurance. No extra insurance is required, as the treatment aligns with standard care practices.

The NAPOLI Study is a retrospective multicenter observational study designed to characterize hormone receptor-negative/low invasive lobular carcinoma of the breast. The study will collect real-world clinicopathological, molecular, therapeutic and outcome data from patients diagnosed and treated at participating centers. The aim is to describe the clinical behavior, pathological features, receptor profile, treatments received and oncologic outcomes of this rare breast cancer subtype.

This study plans to enroll participants with previously treated metastatic pancreatic cancer and harbor centrally confirmed KRAS G12D mutation. These participants are required to experience disease progression on or after at least one prior standard systemic therapy containing fluorouracil or gemcitabine, and either progressed on or were intolerant to the last treatment. Eligible participants will be randomized 1:1 to the experimental group or the control group for treatment.

This study is for people who have anal cancer and have not yet had treatment. The regular treatment for people who have anal cancer is chemoradiation therapy (CRT). CRT is when chemotherapy and radiation therapy are given at the same time. Studies show that CRT works well to treat anal cancer and prevents many people from needing surgery which may require a colostomy bag. Doctors know that CRT is an effective way to treat anal cancer. But, they are doing studies to find out how much dose of radiation and chemotherapy should be given during the CRT. Higher doses of chemotherapy and radiation could increase the risk of side effects, but lowering the dose of chemoradiation has the risk of not being as effective to treat the cancer. One way to predict whether participants need higher or lower doses of radiation therapy is to do a blood test called ctDNA (circulating tumor DNA) to test for the presence of human papillomavirus (HPV). This test is done at certain times while participants are getting CRT. This has been shown to be a marker for the presence of anal cancer. In this study, doctors will tailor lower versus higher doses of CRT based on the tumor response that is measured by ctDNA. The purpose of this study is to see if customizing the dose of chemoradiation based on the amount of ctDNA will increase survival in participants with anal cancer and/or decrease the risk of side effects. Some participants in this study whose cancer does not respond as well to the CRT may have the opportunity to receive a drug called Retifanlimab that stimulates the body's immune system. Retifanlimab is approved by the Federal Drug Administration (FDA) for treating anal cancer that is recurrent or metastatic since there is proven benefit in these situations.

This clinical trial tests how well a digital treatment platform using a mobile application works for the delivery of home-based sequential therapy in patients with glioma. Access to specialized neuro-oncology care in the United States for patients with glioma is critically deficient. Care at centers with neuro-oncology specialists is associated with improved survival outcomes, yet many patients have limited access due to distance, disease-related disability, or lack of financial resources. The application provides patients continuous access to their care team in the home setting. A digital treatment platform may increase clinical trial participation and accelerate development of novel therapeutics while addressing a great health disparity in patients with glioma.

The aim of the CORRECT phase 2 study is to show non-inferiority of Contact x-ray brachytherapy (CXB) + short-course radiotherapy (SCRT) compared to the experimental arm of the OPERA trial in organ preservation for early and early intermediate rectal cancer (cT1-3abN1).

Despite the progress in the therapy, Hodgkin's Lymphoma (HL) remains fatal for more than 15% of patients. Even in patients who are cured, the morbidity of therapy is substantial and long-lasting. New therapeutic agents are required therefore not only to further reduce mortality but also to alleviate morbidity. The majority of HL express the CD30 antigens. CD30 expression is routinely used for the diagnosis of HL. Preclinical observations support CD30 as a viable target of CAR-T therapy. This phase Ib/II study was conducted based on these observations. The purpose of this study is to determine the tolerability of ATLCAR.CD30.CCR4 cells in subjects with Hodgkin's Lymphoma and identify a recommended dose for further. This is a single-center, open-label phase Ib/II trial that uses a 3+3 design to identify a recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells in Hodgkin's Lymphoma. The phase II portion is designed to determine the PFS of ATLCAR.CD30.CCR4 in Hodgkin's Lymphoma. Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments.

This study investigates the changes in positron emission tomography (PET)/computed tomography (CT) imaging scans during chemoimmunotherapy and radiation therapy treatment in patients with stage IV non-small cell lung cancer. Analyzing changes in PET/CT imaging scans may help doctors assess and predict patterns of cancer response to chemoimmunotherapy and radiation therapy.

This study is a single-center, single-arm, prospective clinical trial designed to evaluate the efficacy of local excision followed by postoperative chemoradiotherapy in patients with early-stage low/ultra-low rectal cancer. The study plans to enroll 60 patients with T1-2N0M0 low/ultra-low rectal cancer.

Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head \& neck cancers

To find out if adding treatment with fecal microbiota transplantation (FMT) is effective at treating gut-related side effects of antibiotic treatment in participants who are receiving standard therapy with anti-CD19 chimeric antigen receptor T-cell (CAR-T cell) therapy.

This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well PF-08634404 works when given alone or with chemotherapy . Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. The study is for adults with Transformed Small Cell Lung Cancer (T-SCLC ). T SCLC is a rare lung cancer that happens when one type of lung cancer changes into a more aggressive type after treatment stops working. To join the study, participants must meet the following conditions: * Are aged 18 years or older * Diagnosed with T-SCLC and have not received treatment for this type of lung cancer (a single cycle of chemotherapy may be permitted) * Prior diagnosis of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with tyrosine kinase inhibitors (TKIs) * Have healthy organs based on medical tests and are in good physical condition After joining the study, adults will be given chemotherapy in addition to the study medicine. After this combination treatment is finished, the study medicine will be continued alone. Adults will receive the treatment through IV infusions (medicine given directly into a vein). All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.

This is a prospective, randomized, open-label, two-arm phase 2 trial that will evaluate whether the use of Pulsed Low-Dose-Rate radiation technique, as compared to standard radiation, is associated with reduced rates of clinically significant esophagitis during and following chemoradiation.

The standard treatment for locally advanced cervical cancer is well established as a combination of chemotherapy and radiation, typically over 25-28 daily fractions with the addition of a brachytherapy boost to the primary tumor. An important component to treatment efficacy is overall treatment time. Prolongation of overall treatment time has been shown to lead to worse local control and overall survival; thus, strategies to effectively deliver radiation efficiently is required. This is a pragmatic feasibility study to determine the impact of upfront brachytherapy combined with hypofractionated external beam radiation for patients with locally advanced cervical cancer (FIGO 2018 stage IB3-IVA) on late gastrointestinal and genitourinary toxicity, oncologic outcomes including recurrence free survival, and systemic and local immune response.