Elizabeth

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to standard chemotherapy, with or without radiation, can improve survival for patients aged 5 to 60 years with newly diagnosed stage I or II classical Hodgkin lymphoma. This phase III trial compares outcomes in groups based on their early response to initial chemotherapy, aiming to understand if immunotherapy can lead to better progression-free survival and overall survival compared to standard treatment alone. The study also looks at side effects, quality of life, and long-term health impacts across different patient groups. Participants first receive two cycles of standard ABVD chemotherapy every 28 days, followed by imaging to classify their response as rapid or slow early responders and their risk status as favorable or unfavorable. Based on these factors, patients are assigned to one of eight treatment arms that include either continued standard chemotherapy regimens or immunotherapy with brentuximab vedotin and nivolumab, sometimes combined with involved-site radiation therapy. Treatments are given intravenously or orally depending on the drugs, and cycles typically last 28 days. Imaging and blood samples are collected regularly throughout the study. Throughout the trial, participants undergo frequent scans such as FDG-PET, CT, MRI, and PET-CT to monitor their disease status. Blood samples and questionnaires assess treatment effects and quality of life. After completing treatment, patients have scheduled follow-up visits every 3 months for the first year, then every 6 months for two years, and annually up to 12 years to track long-term outcomes, side effects, and survival. The main measurements focus on progression-free survival, overall survival, treatment-related adverse events, and patient-reported experiences.

Researchers are investigating the addition of an immunotherapy drug called durvalumab to standard chemotherapy treatment in patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial aims to compare the effectiveness of usual chemotherapy alone versus chemotherapy combined with durvalumab. Immunotherapy with durvalumab may help the immune system attack cancer cells and prevent tumor growth and spread, while chemotherapy drugs like paclitaxel, doxorubicin, and cyclophosphamide work to stop cancer cells from growing or dividing. Previous studies suggest patients with an MP2 result might respond better to this combined treatment approach. Participants first undergo MammaPrint testing to confirm MP2 status before randomization into two groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide intravenously on day 1 every 14 days for 4 cycles. The other group receives the same chemotherapy schedule plus durvalumab intravenously over 60 minutes on specified cycles during both chemotherapy phases. Mammography is performed during screening, and optional tissue and blood samples are collected for future studies. Throughout the study, participants are monitored through various assessments including imaging, physical exams, laboratory tests, and quality of life questionnaires focusing on fatigue and physical and mental health. Researchers track breast cancer event-free survival and other outcomes such as treatment side effects and response rates. After completing treatment, patients are followed for up to 10 years or until death to evaluate long-term outcomes and safety.

Researchers are evaluating a new treatment schedule for patients with advanced lung or head and neck cancers. This study focuses on alternating cycles of combined chemotherapy and immunotherapy with immunotherapy alone during the initial treatment phase. The goal is to see if less frequent chemotherapy, given once every six weeks instead of every three weeks, can effectively control cancer while maintaining quality of life. This is a three-arm, parallel phase II study assessing the safety, tolerability, and effectiveness of these treatments. The study involves three treatment groups receiving different combinations of chemotherapy drugs (including Paclitaxel, Pemetrexed, 5Fluorouracil, Carboplatin) and the immunotherapy drug Pembrolizumab. Treatment during the induction phase alternates between chemoimmunotherapy and immunotherapy alone to reduce chemotherapy exposure. Patients with specific types of lung or head and neck cancers are assigned to different study arms based on cancer histology. Treatment cycles vary up to six cycles for head and neck cancer patients. Participants will undergo assessments including imaging and laboratory tests before and during treatment to evaluate tumor response and safety. Researchers will track the percentage of patients completing chemotherapy cycles, response rates at six weeks, and the best overall response. Safety and tolerability of the treatments will also be monitored throughout the study. The study requires informed consent and regular clinical evaluations to ensure participant health and study compliance.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer after surgery by using the presence or absence of circulating tumor DNA (ctDNA) in the blood. This approach aims to identify microscopic residual tumor cells and may provide better risk prediction for cancer recurrence compared to traditional methods. The trial focuses on patients with Stage IIB, IIC, or III colon cancer who have undergone complete tumor removal. Participants will have their tumor tissue and blood tested centrally using the Signatera assay to determine ctDNA status. Patients without detectable ctDNA may avoid chemotherapy, while those with detectable ctDNA are considered at higher risk and will be randomly assigned to receive different chemotherapy regimens, including mFOLFOX6, CAPOX, or mFOLFIRINOX, given intravenously or orally over periods ranging from 3 to 6 months. The study includes initial screening, treatment, and possible second randomization for patients whose ctDNA status changes during monitoring. During the study, participants will undergo various assessments including blood tests, imaging scans, and performance evaluations to monitor their health and response to therapy. Researchers will track the time to ctDNA positivity and disease-free survival for up to 3 and 5 years, respectively. Safety and treatment effects will be closely observed throughout the study duration, ensuring thorough follow-up and monitoring for all participants.

Researchers are evaluating the safety and effectiveness of adjusting fluoropyrimidine chemotherapy doses based on genetic testing for DPYD variants. Fluoropyrimidines like 5-Fluorouracil and Capecitabine are important treatments for cancers such as colorectal, breast, head and neck, and gastrointestinal cancers. This Phase 4 study focuses on patients with a single DPYD gene variant (heterozygotes) to compare reduced dosing guided by genetic results versus standard dosing in patients without these variants, aiming to reduce severe treatment-related toxicities. The study involves two groups: one with DPYD heterozygous variants receiving a reduced dose of fluoropyrimidines, and a control group with normal DPYD genes receiving standard dosing. Treatments include Fluorouracil injection and Xeloda (Capecitabine), with possible dose escalation to 75% or 100% if well tolerated. DPYD testing is done before starting chemotherapy to assign participants appropriately. The study includes patients receiving first-line therapy, including FOLFOX regimen, and monitors dosing adjustments based on tolerance. Participants will be assessed for the occurrence of severe fluoropyrimidine-related toxicities over 24 months. Researchers will monitor treatment effects through clinical evaluations and genetic testing results. Inclusion criteria require confirmed cancer diagnosis and DPYD testing from certified labs before treatment. The study excludes patients who cannot receive fluoropyrimidines or have multiple DPYD variants, as well as pregnant women and children. The trial aims to provide real-world validation of DPYD-guided dosing strategies to better balance safety and treatment effectiveness.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating surgical and minimally invasive treatments for lumbar spinal stenosis (LSS) by comparing Medicare patients who received the MILD procedure against those who had interspinous process decompression (IPD). The study focuses on outcomes such as the rate of harms related to the initial procedure and the frequency of additional surgical or minimally invasive interventions within 24 months after treatment. Enrollment includes patients treated from January 1, 2017, onward, with continuation until the sponsor decides to stop. The MILD procedure involves percutaneous image-guided lumbar decompression, performed under fluoroscopy through a dorsal approach to partially remove tissue and bone at the affected spinal level. The control group receives the IPD procedure for LSS. Both groups are monitored for a 24-month period post-index procedure using Medicare claims data to track reoperations and any harms. Participants contribute data through Medicare claims without needing prior enrollment or consent, as the study is exempt from IRB oversight. Researchers collect and analyze information on procedure-related harms and subsequent interventions over two years. This approach allows evaluation of long-term safety and effectiveness outcomes for patients treated with either MILD or IPD.

Researchers are evaluating an adaptive phase 2 study to improve neoadjuvant therapy for patients with stage II-III HER2-positive early-stage breast cancer. This study uses a novel molecular phosphoprotein-based biomarker assay called HER2 Activation Response Predictive Signature (HARPS) to identify HARPS-positive and HARPS-negative tumors. The study also aims to assess 3-year invasive disease-free survival (iDFS), correlate changes in circulating tumor DNA (ctDNA) with treatment outcomes, and understand quality of life changes in patients treated with an adaptive neoadjuvant approach. Patients with HARPS-positive HER2-positive cancer will receive dual HER2-targeted therapy with trastuzumab and pertuzumab for 3 cycles. If treatment response is observed via ctDNA and MRI, they continue with 6 cycles of the same therapy. If no response after 6 weeks, chemotherapy with docetaxel, paclitaxel, or Abraxane is added for 4 cycles followed by 2 cycles of trastuzumab and pertuzumab before surgery. Patients with HARPS-negative tumors and detectable ctDNA at diagnosis receive 4 cycles of taxane, platinum, trastuzumab, and pertuzumab, monitored for ctDNA clearance. If cleared, they get 2 more cycles before surgery; if not, therapy is escalated with anthracycline-based treatment or trastuzumab deruxtecan (T-DXD). Participants will undergo tumor testing, ctDNA collection, breast MRI, and quality of life assessments throughout the study. Researchers will monitor treatment-emergent adverse events up to 36 months. The study plans to enroll 50 patients and track invasive disease-free survival over three years while assessing treatment safety and patient well-being.

Researchers are investigating whether observation is as effective as continuing pembrolizumab treatment in patients with early-stage triple-negative breast cancer who achieved a complete response after preoperative chemotherapy combined with pembrolizumab. This phase III trial aims to evaluate recurrence-free survival and quality of life, as well as the value of reducing immunotherapy treatment after surgery in these patients. The study also examines differences in adverse events, overall survival, and financial impacts between treatment approaches. Participants are randomly assigned to one of two groups after completing neoadjuvant chemotherapy with pembrolizumab and surgery. One group receives pembrolizumab intravenously as adjuvant therapy, while the other group undergoes observation without further treatment. Both groups have tumor biopsies and blood samples collected on study and during follow-up. Additional assessments include questionnaires and quality-of-life evaluations. During the study, researchers monitor participants for up to 10 years to measure recurrence-free survival. They assess quality of life using validated tools, track adverse events, and evaluate financial toxicity and work productivity. The study includes tumor tissue analysis, blood sample collection, and patient-reported outcomes to understand the long-term effects and value of treatment de-escalation in breast cancer care.

Researchers are evaluating the effectiveness of using brain magnetic resonance imaging (MRI) scans alone compared to combining MRI scans with prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC). This phase III trial aims to determine if MRI surveillance alone is not worse than adding PCI in terms of overall survival. The study also looks at cognitive function, brain metastasis-free survival, and treatment side effects among patients with limited or extensive-stage SCLC. Participants are randomly assigned to one of two groups. One group receives PCI, which is radiation therapy focused on the brain, given over two weeks for 20 minutes per day, five days a week, along with scheduled MRI scans at 3, 6, 9, 12, 18, and 24 months. The other group undergoes MRI scans at the same intervals without receiving PCI. Both groups are monitored closely through these MRI scans to track any spread of cancer to the brain. During the study, patients will have regular MRI scans, cognitive assessments, and evaluations of side effects and survival outcomes up to two years after randomization. Blood samples will be collected for future research. Researchers will monitor overall survival, cognitive failure rates, and brain metastasis occurrence, aiming to understand if avoiding PCI might reduce side effects without compromising survival. Participant involvement includes multiple scheduled scans and tests over a two-year follow-up period.