CIty of Hope

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 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 how well venetoclax works in treating patients with relapsed hairy cell leukemia or its variant. This phase II trial focuses on patients whose disease has returned after previous improvement and aims to measure the response rates, including complete remission and minimal residual disease-negative status. The study also explores how genetic mutations may relate to treatment response and evaluates the safety of venetoclax in this patient group. Participants receive venetoclax by mouth once daily on days 1 through 28 of each 28-day cycle. Treatment may continue for up to 19 cycles unless the disease progresses or unacceptable side effects occur. During the study, patients undergo imaging scans like CT or MRI and blood tests regularly. Bone marrow biopsies or aspirations may also be performed, and those with central nervous system involvement may have lumbar punctures throughout the trial. Participants are monitored closely with various tests including blood samples, imaging, and possibly bone marrow and cerebrospinal fluid assessments. After finishing treatment, patients have a follow-up visit at 30 days to assess outcomes. Researchers measure the objective response rate up to 30 days after the last dose, along with remission rates, minimal residual disease status, duration of response, and safety events over this period.

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 evaluating the effect of adding the drug tivozanib to the immunotherapy pembrolizumab compared to pembrolizumab alone in patients with high-risk renal cell carcinoma RCC. The study aims to determine whether this combination improves disease-free survival and overall survival. This phase III trial also assesses side effects, quality of life, and collects specimens for future research in patients who have undergone surgery to remove all known kidney cancer sites. In this study, participants are randomly assigned to one of two groups. One group receives pembrolizumab intravenously on specific days of each 12-week cycle for up to 4 cycles. The other group receives the same pembrolizumab schedule combined with oral tivozanib taken daily on specific days within the 12-week cycle for up to 6 months. Throughout the trial, participants undergo blood samples, MRI or CT scans, and may have tissue biopsies. After treatment, patients are followed regularly for up to 10 years to monitor outcomes. Participants will have scheduled visits during treatment cycles and follow-up visits every 4 months for 2 years, then every 6 months for 3 years, and annually for 5 more years. The research team measures disease recurrence or death disease-free survival as the main outcome, along with overall survival, side effects, treatment tolerance, and quality of life. Safety monitoring and quality of life assessments are included to evaluate the impact of the treatments over the long term.

Researchers are evaluating elacestrant compared to standard endocrine therapies in adults with node-positive, Estrogen Receptor-positive ER, HER2-negative early breast cancer who are at high risk of cancer returning. The study focuses on those who have had prior endocrine therapy and aims to measure how well elacestrant may prevent invasive breast cancer recurrence over five years. Participants are randomly assigned to receive either 345 mg of elacestrant daily for five years or continue their prior standard endocrine therapy, which may include an aromatase inhibitor anastrozole, letrozole, or exemestane or tamoxifen. The trial is open-label, meaning both participants and researchers know which treatment is given. During the study, participants will have regular assessments to monitor cancer recurrence, survival, side effects, and quality of life. Evaluations include questionnaires on health status and physical functioning at baseline, six months, and annually for up to five years. Safety is tracked through adverse event reporting up to five years plus 28 days. The total participation duration can last up to five years with ongoing monitoring and data collection.

Researchers are investigating whether adding the drug Docetaxel to the usual hormone treatments, Androgen Deprivation Therapy ADT and Androgen-Receptor Pathway Inhibitor ARPI, can better control metastatic castration sensitive prostate cancer in men who have not responded optimally to initial hormone therapy. This phase III, international, open-label, randomized trial seeks to compare the effectiveness of this combined approach against the standard hormone therapy alone. Participants will be randomly assigned to receive either the standard hormone therapy with ADT plus ARPI or the same hormone therapy combined with Docetaxel chemotherapy. The trial focuses on men with metastatic prostate cancer who continue to have elevated PSA levels after 6 to 12 months of hormone-targeting treatment. Treatments are administered according to physician choice and assignment, and the study evaluates outcomes over a long period. During the trial, participants will be closely monitored with assessments including PSA levels and clinical progression over 39 months. Researchers will measure overall survival as the primary outcome, along with secondary outcomes such as PSA progression, PSA response, PSA kinetics, and progression-free survival. Participants must be accessible for treatment and follow-up to allow for complete documentation of treatment effects and adverse events throughout the study duration.

Researchers are evaluating how well a type of radiation therapy called photon volumetric modulated arc radiotherapy VMAT craniospinal irradiation CSI works for patients with breast cancer or non-small cell lung cancer NSCLC that has spread to the cerebrospinal fluid and meninges, causing leptomeningeal disease. This phase II trial aims to assess the treatments effectiveness in controlling cancer in the central nervous system and its impact on patient quality of life and side effects. The study also explores biological markers related to inflammation and genetic predictors of disease progression. Participants receive photon-VMAT-CSI once daily for 10 treatments over 10 to 20 days Monday through Friday, provided there is no disease progression or unacceptable side effects. Before and after treatment, patients undergo MRI scans, blood draws, and cerebrospinal fluid collection through lumbar puncture or Ommaya reservoir tap. These procedures help monitor treatment response and collect samples for exploring biological markers. During the study, patients complete questionnaires assessing quality of life, anxiety, and cognitive function at multiple time points, including baseline, one month after treatment, and every three months up to one year. Researchers track central nervous system progression-free survival, overall survival, radiographic response, and treatment toxicities. Follow-up visits occur one month after treatment and then every three months for up to a year to monitor disease status and patient well-being.

Researchers are evaluating the effect of adding a live biotherapeutic product called CBM588 to pembrolizumab compared to pembrolizumab alone in preventing the return of renal cell cancer after surgery. Pembrolizumab is an immune checkpoint inhibitor used after surgery for renal cell cancer. This phase II trial investigates whether changes to the bodys microbiome caused by CBM588 can improve response to immunotherapy and reduce cancer recurrence. Participants are randomly assigned to one of two groups. One group receives CBM588 orally twice daily on days 1-21 or 1-42 of each treatment cycle along with pembrolizumab given intravenously on day 1 of each cycle. The other group receives pembrolizumab alone intravenously on day 1 of each cycle. Treatment cycles repeat every 21 or 42 days for up to 12 months unless disease worsens or unacceptable side effects occur. Blood samples and computed tomography scans are collected throughout the study. During the trial, participants will undergo regular imaging and blood tests to monitor immune and microbiome changes. Researchers will measure changes in interleukin-12 levels, recurrence-free survival, overall survival, stool microbiome diversity, immune cell populations, and cytokines. Safety is monitored up to 30 days after the last dose. After completing treatment, participants have a follow-up visit at 30 days. The study is expected to continue until October 2028.

Researchers are studying patients with stage II-IV colorectal cancer CRC that can be removed by surgery to compare two blood tests, the Haystack MRD test and the Signatera assay, for detecting if the cancer returns after treatment. The study aims to find if the Haystack test can detect cancer recurrence earlier and more sensitively than the currently used Signatera test. Early detection of cancer return is important to improve chances for curative treatment in these patients. Participants will provide tissue and blood samples before surgery and then undergo both Haystack MRD and Signatera ctDNAcfDNA testing several times after surgery. Testing occurs 3 to 10 weeks post-surgery, then every 3 months for the first two years, and every 6 months for years three to five if no disease progression is observed. The study also explores the performance of two additional cancer detection assays under development. Throughout the study, participants will have blood samples collected at regular intervals and archival tissue accessed for personalized testing. Researchers will monitor minimal residual disease rates, the timing of cancer recurrence detection by the tests and imaging, and associations between ctDNA results and recurrence status over a follow-up period of up to five years. This long-term monitoring aims to assess the clinical performance and lead time advantages of the Haystack test compared to Signatera.