Mitchell

This research aims to evaluate the effectiveness and safety of a combination of three drugsinavolisib, ribociclib, and fulvestrantcompared to a placebo combined with ribociclib and fulvestrant. It focuses on people with advanced breast cancer that is resistant to endocrine therapy, specifically those with hormone receptor-positive, HER2-negative disease who have certain genetic markers related to chromosome 8p loss and no PIK3CA mutation. The study is conducted as a phase II, randomized, double-blind, placebo-controlled trial to explore treatment options in this patient group. Participants are randomly assigned to receive either inavolisib along with ribociclib and fulvestrant or a placebo with ribociclib and fulvestrant. Each drug is given according to a specific schedule outlined in the study protocol, though exact dosing details are not provided here. This setup allows researchers to compare the results and safety profiles of the combination treatment against the placebo combination over the course of the study. Throughout the trial, participants undergo regular assessments to measure treatment response, including the percentage of participants with confirmed objective response, progression-free survival, overall survival, duration of response, and clinical benefit rate. The study also tracks adverse events and patient-reported side effects using validated questionnaires. These evaluations may continue for up to approximately two years, ensuring thorough monitoring of both effectiveness and safety during the participants involvement.

Researchers are evaluating the effectiveness of pembrolizumab combined with sacituzumab govitecan-hziy compared to standard chemotherapy treatments in patients with advanced urothelial cancer that has spread locally or to other parts of the body. This phase III trial focuses on patients whose cancer has not responded to prior anti-PDL1 therapy. The study aims to compare overall survival, progression-free survival, response rates, duration of response, treatment side effects, and quality of life between the new combination therapy and usual chemotherapy care. Participants are randomly assigned to one of two treatment groups. One group receives standard chemotherapy options such as carboplatin or cisplatin with gemcitabine, or alternatively docetaxel or paclitaxel, given intravenously in 21-day cycles for up to six cycles or until disease progression or unacceptable side effects. The other group receives pembrolizumab intravenously on day 1 and sacituzumab govitecan-hziy intravenously on days 1 and 8 every 21 days for up to 35 cycles or two years, unless disease progresses or side effects become unacceptable. Both groups undergo blood tests and imaging scans like CT or MRI throughout the study. During the trial, participants will have regular assessments including blood sample collection and imaging to monitor their cancer status and treatment effects. Researchers will also evaluate patient-reported quality of life and fatigue at multiple time points up to 12 months. After completing treatment, participants are followed up 30 days later and then annually for five years to track survival and health outcomes. This comprehensive approach helps researchers understand both the clinical outcomes and the impact on patients well-being over time.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating the efficacy and safety of opevesostat combined with daily corticosteroids compared to alternative treatments abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer mCRPC who have previously been treated with one next-generation hormonal agent NHA. The study aims to determine if opevesostat offers better control of disease progression assessed by radiographic progression-free survival, including participants with and without androgen receptor ligand binding domain mutations. Overall survival has also been included as a secondary outcome measure. Participants are randomly assigned to one of two groups. One group receives opevesostat 5 mg orally twice daily, plus dexamethasone 1.5 mg and fludrocortisone acetate 0.1 mg orally once daily, continuing until disease progression. Hydrocortisone is available as a rescue medication if needed. The other group receives either abiraterone 1000 mg once daily with prednisone 5 mg twice daily or enzalutamide 160 mg once daily, also until disease progression. This open-label, phase 3 study compares these two treatment approaches in a parallel design. During the study, participants undergo regular assessments including imaging scans to measure disease progression, safety monitoring, and evaluations of overall survival and quality of life. Researchers track radiographic progression-free survival for up to 52 months and secondary outcomes such as overall survival, time to new treatments, pain progression, and prostate-specific antigen PSA responses for up to approximately 82 months. Participants are closely monitored for adverse events and treatment tolerability throughout the study duration, which spans several years.

Researchers are investigating the wide range of molecular features found in people receiving care within a large community healthcare system who are at risk of or diagnosed with cancer. The study aims to understand the genetic factors behind premalignant and malignant conditions across various cancer types and stages. This research helps advance knowledge of cancer biology and supports the discovery of biomarkers linked to clinical outcomes. Participants will undergo comprehensive molecular profiling, including somatic tumor testing from tissue andor blood samples using next-generation sequencing. Some samples may also receive whole exome or transcriptome sequencing for research purposes. Pharmacogenomic testing will help explore how individuals respond differently to medications, and participants may optionally provide microbiome samples. Participants may also consent to store biological samples in a biobank and allow their de-identified data to be used for future research. During the study, electronic health records will be reviewed both retrospectively and prospectively to connect clinical data with genomic findings. Researchers will measure how many patients undergo molecular profiling, are referred for genetic testing or targeted clinical trials, and have therapy changes based on molecular or pharmacogenomic results. The study spans five years, with long-term follow-up and data collection to support ongoing research and collaboration in cancer studies.

Researchers are evaluating how to best recommend chemotherapy for patients with Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.

Researchers are studying premenopausal women with early-stage breast cancer that is estrogen receptor-positive and HER2-negative, focusing on tumors with specific gene recurrence scores. The trial aims to find out if adding chemotherapy to ovarian function suppression plus endocrine therapy improves invasive breast cancer-free survival compared to ovarian function suppression plus endocrine therapy alone. This Phase III trial addresses the need for better treatments in younger women, given their higher risk and past conflicting study results on ovarian suppression and chemotherapy. Participants are randomly assigned to one of two groups one receiving ovarian function suppression combined with an aromatase inhibitor for five years, and the other receiving adjuvant chemotherapy followed by the same ovarian function suppression and aromatase inhibitor regimen. Choices for the aromatase inhibitor and gonadotropin releasing hormone agonist are made by the investigator, with options including drugs such as goserelin, leuprolide, or triptorelin. Endocrine treatment beyond five years is at the investigators discretion, and bilateral oophorectomy may be used instead of ovarian suppression if preferred. During the study, participants are monitored over 11 years from randomization, with measurements including invasive breast cancer-free survival as the primary outcome. Secondary outcomes include disease-free survival, overall survival, recurrence intervals, menopausal symptoms, and pain during aromatase inhibitor therapy. Safety and treatment effects are assessed through regular evaluations, and participants continue to be followed long term to understand the impact of treatments on their breast cancer outcomes.

Researchers are comparing two chemotherapy combinations for treating advanced, unresectable, or metastatic HER2 negative adenocarcinomas of the esophagus, gastroesophageal junction, and stomach. This phase III trial evaluates modified FOLFIRINOX fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan with or without nivolumab versus modified FOLFOX fluorouracil, leucovorin calcium, and oxaliplatin with or without nivolumab. Chemotherapy drugs act to stop tumor growth by killing cells or stopping division, and immunotherapy with nivolumab may affect the immune system to hinder tumor growth and spread. Participants are randomized into two groups one receives mFOLFIRINOX plus nivolumab as clinically indicated, and the other receives mFOLFOX plus nivolumab as clinically indicated. Treatments are administered intravenously. Throughout the study, participants undergo magnetic resonance imaging MRI, computed tomography CT scans, and may provide blood samples. Nivolumab is given as needed based on clinical assessment during the trial. Participants will be monitored up to 2 years from randomization for overall survival, with secondary measures including progression-free survival, response rates, duration of response, adverse events, and patient-reported outcomes collected at baseline and during treatment cycles. Safety and tolerability are evaluated, and exploratory analyses include biomarker assessments such as PD-L1 combined positive score and cell-free DNA. The trial includes regular imaging and clinical assessments to track disease status and treatment effects.

Researchers are evaluating whether simply observing patients after surgery is as effective as continuing pembrolizumab treatment in preventing cancer recurrence in people with early-stage triple-negative breast cancer TNBC who had a complete response after receiving chemotherapy plus pembrolizumab before surgery. This Phase III trial aims to determine if stopping pembrolizumab post-surgery can maintain recurrence-free survival while potentially improving quality of life and reducing treatment burden. Participants are randomly assigned to one of two groups after finishing chemotherapy with pembrolizumab and surgery. One group continues pembrolizumab intravenously every 3 or 6 weeks for 27 weeks. The other group undergoes observation without further pembrolizumab for the same period. Throughout the study, patients have tumor biopsies and blood collected, along with imaging such as mammography, breast ultrasound, or MRI during follow-up. Participants will be monitored for recurrence-free survival and overall survival for up to 10 years. The study also assesses adverse events, quality of life, financial impact, and work productivity at about 27 weeks after starting the assigned treatment or observation. Safety and treatment effects are tracked through biopsies, imaging, blood tests, and patient questionnaires during the study and follow-up.

Researchers are evaluating a new medicine called PF-08634404 combined with chemotherapy for adults with colorectal cancer that has spread to other parts of the body. The study aims to understand how well this new combination works compared to an existing treatment using Bevacizumab with chemotherapy. The study is a phase 3, double-blind, randomized trial focusing on treatment effectiveness and safety in participants who have not received prior systemic therapy for metastatic disease. Participants are randomly assigned to one of two groups. One group receives PF-08634404 with chemotherapy, and the other group receives Bevacizumab with chemotherapy. Both treatments are given through intravenous IV infusions in cycles. Treatment continues as long as it helps and side effects are manageable. Treatments are administered at clinical sites by trained staff. Participants will have regular visits for treatment, health evaluations, and various tests. After stopping treatment, there is a follow-up visit about 30 to 37 days later to review health and side effects. Further follow-up occurs every 12 weeks by phone, in person, or via health record review to monitor health status and any new treatments. The study duration for each participant is approximately 33 months. Researchers will measure progression-free survival, overall survival, response rates, quality of life, and monitor safety throughout the study.