University of Winsconsin Carbone Cancer Center-Eastpark medical Center

Researchers are evaluating the safety, side effects, and best dose of a combination of two anti-cancer drugs, neratinib and trastuzumab deruxtecan, in patients with advanced solid tumors that have spread or cannot be removed by surgery and have changes in the HER2 gene. This phase I trial aims to determine the maximum tolerated dose, assess tumor response, and study the drugs effects on tumor markers and overall survival in this patient population. Participants receive neratinib orally once daily on specified days of each 21-day cycle and trastuzumab deruxtecan intravenously over 30 to 90 minutes on day 1 of each cycle. Treatment cycles repeat every 21 days unless disease progression or unacceptable side effects occur. The study includes dose-escalation and dose-expansion phases, with possible tissue biopsies at various points to evaluate tumor changes and drug impact. Throughout the study, participants undergo blood sample collection, CT scans, and heart function tests via echocardiography or MUGA scans. Biopsies may be performed at baseline, during the study, or at disease progression depending on the cohort. After treatment ends, patients are followed every three months for at least one year to monitor health and survival outcomes. Researchers measure treatment safety, tumor response rates, duration of response, progression-free survival, and drug concentrations over this period.

Researchers are evaluating the addition of pembrolizumab immunotherapy to standard chemotherapy for patients with stage IIA, IIB, IIIA, or IIIB non-small cell lung cancer NSCLC that has been completely removed by surgery. This phase III trial aims to compare disease-free survival and overall survival among different treatment approaches, including chemotherapy alone, chemotherapy followed by pembrolizumab, and chemotherapy combined with pembrolizumab. The study also assesses quality of life and adverse event rates in these patient groups. Participants are randomly assigned to one of three groups. One group receives only chemotherapy with observation afterward. The other two groups receive chemotherapy followed by pembrolizumab or chemotherapy combined with pembrolizumab. Chemotherapy involves one of four platinum doublet regimens administered every 21 days for four cycles, depending on the physicians choice. Pembrolizumab is given intravenously over 25-40 minutes, either after chemotherapy or alongside it, repeated every 21 days or every 6 weeks for multiple cycles. Patients also undergo heart ultrasound, MRI, CT scans, and blood sample collections as part of the study. During the trial, participants have regular medical assessments including imaging and blood tests to monitor their health. Follow-up visits occur 6 weeks after treatment, then every 3 months for 2 years, every 6 months for years 2-4, and annually up to 10 years from randomization. Researchers measure disease-free survival as the main outcome, tracking the time until cancer recurrence or death. They also evaluate overall survival, side effects, drug tolerability, and patient-reported quality of life over time.

Researchers are investigating treatments for men with prostate cancer that has returned after surgery, focusing on those who experience a rise in prostate-specific antigen PSA levels, indicating biochemical recurrence. The study examines whether adding enhanced systemic therapy apalutamide combined with abiraterone and prednisone to standard care, which includes prostate radiation therapy and short-term androgen deprivation, improves outcomes. Additionally, for patients whose cancer has spread beyond the pelvis as detected by PET imaging, the study evaluates the benefit of adding metastasis-directed radiation therapy. Participants undergo baseline PETCT or PETMR scans to determine the extent of cancer spread. Based on these results, they are randomized into one of four treatment arms standard radiation with androgen deprivation, enhanced therapy including apalutamide, or enhanced therapy plus targeted radiation for metastatic disease. Treatments involve various forms of radiation therapy, androgen deprivation drugs, and oral apalutamide, administered over six months in the absence of disease progression or unacceptable side effects. Some patients may receive repeat PET scans to assess treatment response. During the study, participants have scheduled assessments including imaging, blood tests measuring PSA levels, and quality-of-life questionnaires over up to ten years. Follow-up visits occur every three months for the first two years, then less frequently up to ten years. Researchers monitor progression-free survival, overall survival, event-free survival, PSA progression, adverse events, and quality of life measures including cognitive function and fatigue. This long-term monitoring aims to determine the effectiveness of the added therapies compared to standard treatment alone.

Researchers are evaluating whether the drugs mosunetuzumab and polatuzumab vedotin can provide benefits for patients with diffuse large B-cell lymphoma or grade 3b follicular lymphoma that has returned or not responded to treatment. This study focuses on patients who have already received chemotherapy with fludarabine and cyclophosphamide, followed by CAR T-cell therapy. The goal is to determine if adding these drugs after previous treatments may better control or shrink the cancer. Participants first receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by one of three CAR T-cell therapies given by infusion tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel. After this, participants are randomly assigned to one of four groups receiving mosunetuzumab alone, polatuzumab vedotin alone, both drugs together, or observation without further drug treatment. Those in the observation group who experience disease progression within 12 months may switch to receive both drugs. Throughout the study, patients undergo PET-CT or CT scans and provide blood and tissue samples for research. Participants will be monitored regularly with imaging scans and laboratory tests to assess disease status and treatment effects. Researchers will measure progression-free survival, overall survival, remission rates, and treatment side effects up to two years. The study also includes collecting and banking tissue samples and PET-CT images for future research. The total length of involvement depends on individual timelines but includes treatment and follow-up periods extending up to two years or more.

Researchers are investigating targeted therapies directed by genetic testing for patients with locally advanced or advanced solid tumors that have spread or progressed after standard treatments. This Phase 2 screening trial, called ComboMATCH, aims to match patients to specific combination treatments based on genetic mutations found in their tumor cells. The study seeks to improve treatment planning by using genetic information to guide therapy choices. Patients undergo tumor genetic screening using previously collected samples or a new biopsy if eligible and aged 18 or older. Based on their tumors genetic profile, patients are assigned to one of multiple treatment subprotocols involving different drug combinations. Treatments include oral, intravenous, and intramuscular drugs such as selumetinib, olaparib, fulvestrant, binimetinib, and others. Treatment cycles generally repeat every 28 days until disease progression or unacceptable toxicity. Patients may also undergo biopsies, blood collection, imaging scans CT, MRI, PET, echocardiograms, and bone marrow procedures as part of the study. Throughout the trial, participants have regular assessments including tumor biopsies, blood draws, imaging tests, and heart function monitoring. These evaluations occur during screening, treatment, and follow-up periods. Researchers measure patient enrollment, assignment to treatment arms, and treatment outcomes over up to 8 years. Safety is monitored via clinical evaluations and diagnostic tests. This comprehensive approach aims to evaluate responses to targeted therapies guided by tumor genetics for advanced solid tumors.

Researchers are evaluating the safety, side effects, and best dose of novobiocin in patients with solid tumors that have alterations in DNA repair genes. Novobiocin is an antibiotic that blocks a protein called DNA polymerase theta, which helps repair damaged DNA in cells. This study focuses on patients with tumors carrying specific gene mutations related to DNA repair, who may or may not have received prior PARP inhibitor treatment. Participants receive novobiocin orally once daily for 5 days followed by 2 days off each week, with treatment cycles repeating every 28 days if the disease does not progress or toxicity is unacceptable. Throughout the study, patients undergo tumor biopsies, medical imaging scans, and blood sample collection. After completing treatment, patients are followed up every 3 to 6 months for 2 years to monitor outcomes. During the trial, researchers monitor the maximum tolerated dose and recommend a phase 2 dose of novobiocin. They also assess anti-tumor activity, safety, tolerability, and pharmacokinetics. Additional analyses include genetic sequencing and gene expression studies on tumor biopsies. Outcome measures include radiological response, progression-free survival, duration of response, and biological effectiveness over up to 2 years of observation.

Researchers are evaluating a phase II trial to study the use of personalized antibody-drug conjugates ADCs for treating patients with advanced or metastatic solid tumors that show high protein expression of Trop-2, nectin-4, or HER2. This trial aims to assess whether targeted treatments with sacituzumab govitecan, enfortumab vedotin, or trastuzumab deruxtecan work based on RNA and protein testing of tumor markers. These ADCs combine monoclonal antibodies with active drugs to target cancer cells more precisely. The study includes a two-step screening process. First, patients existing RNA test results are reviewed for expression of targets of interest TOIs. Then, protein expression is confirmed by immunohistochemistry IHC on previously collected tissue. Patients with high expression are assigned to one of three treatment cohorts receiving the corresponding ADC drug intravenously on specific schedules sacituzumab govitecan on days 1 and 8 every 21 days enfortumab vedotin on days 1, 8, and 15 every 28 days and trastuzumab deruxtecan on day 1 every 21 days. Imaging scans, biopsies, and blood sample collections are performed throughout the trial, with optional samples taken at progression. Echocardiography or MUGA scans are also used for patients receiving trastuzumab deruxtecan. Participants will undergo thorough assessments including CT and MRI imaging, tumor biopsies before and during treatment, blood collections, and heart function monitoring as applicable. Researchers will measure tumor response rates, progression-free survival, overall survival, molecular markers, and adverse events. After treatment ends, patients will be followed for up to three years with regular check-ins every 3 to 6 months to monitor outcomes and safety. This comprehensive monitoring helps understand the therapys impact and tumor changes over time.

Researchers are evaluating whether adding paclitaxel chemotherapy directly into the abdominal cavity, alongside chemotherapy given through a vein, can better control the spread or growth of gastric cancer that has spread to the abdominal cavity. The study compares this combination approach to the usual chemotherapy treatment for this cancer type. The trial includes a surgical procedure called diagnostic laparoscopy to examine the abdomen and determine the appropriate treatment group for each participant. Participants will undergo diagnostic laparoscopy under general anesthesia, during which they will be randomly assigned to one of two groups. One group receives standard chemotherapy through the vein alone, while the other group receives the same chemotherapy plus paclitaxel delivered directly into the abdomen via an intraperitoneal port placed during surgery. Treatment cycles occur every 21 days for four cycles, with assessments after three months to decide whether to continue treatment or consider surgery to remove the cancer if possible. During the study, participants will have regular imaging scans such as CT or MRI to monitor disease status and blood samples collected periodically. After completing treatment, follow-up visits occur every three months for the first two years and then every six months up to five years to watch for side effects and cancer progression. Researchers will measure progression-free survival and overall survival to evaluate the treatments, along with monitoring adverse events related to the therapy.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase IIIII trial aims to develop a genomic screening method for large cancer populations and assign participants to appropriate sub-studies based on specific cancer biomarkers. The goal is to compare new targeted therapies designed to block cancer growth or spread with standard care, including sub-studies for patients not eligible for biomarker-driven treatments. The study involves screening patient specimens to determine eligibility for various biomarker-driven or non-matched sub-studies within the Lung-MAP umbrella protocol. This is a screening study without direct interventions instead, patients are assigned to different treatment sub-studies, each operating independently. The protocol also includes an optional ancillary study evaluating attitudes about the return of somatic mutation findings suggestive of germline mutations. Participants provide tumor tissue for biomarker testing, including molecular profiling and PD-L1 analysis, and may submit fresh biopsies and blood samples for circulating tumor DNA testing. Researchers will monitor screening success rates up to three years and collect patient and physician feedback on genetic findings. Participation involves signing informed consent, providing smoking history, and possibly completing surveys. The study duration and assessments vary depending on sub-study assignment and patient progression.

Researchers are studying patients with stage II primary invasive cutaneous melanoma to compare the effects of two different surgical excision margins 1cm versus 2cm. The goal is to determine if narrower margins are as safe as wider margins in preventing melanoma recurrence and if they can improve patients quality of life. This trial also looks at the impact of these excision sizes on health services and society. Participants will be randomly assigned to receive either a 1cm or 2cm wide local excision margin around the primary melanoma lesion. Both groups will undergo sentinel lymph node biopsy and may have reconstruction surgery if needed. The surgery must be done within 120 days of diagnosis and within 28 days of randomization. During the study, participants will be followed for up to 60 months to measure disease-free survival as the primary outcome. Additional assessments include local recurrence, distant disease-free survival, melanoma-specific and overall survival, quality of life questionnaires, neuropathic pain evaluations, adverse event monitoring, and health economic analysis. Follow-up questionnaires and safety checks will occur at multiple time points up to 24 months after surgery, with longer-term monitoring continuing up to 120 months.