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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 the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab in patients with advanced or locally unresectable stomach or esophageal adenocarcinoma. This phase II/III trial aims to determine if adding nivolumab improves progression-free survival and overall survival compared to paclitaxel and ramucirumab alone. The study also assesses response rates, disease control, safety, tolerability, and quality of life in participants with PD-L1 CPS 21 1 advanced gastric or esophageal cancer. Participants are randomly assigned to one of two treatment groups. The first group receives nivolumab IV on day 1 of each 28-day cycle, ramucirumab IV on days 1 and 15, and paclitaxel IV on days 1, 8, and 15. The second group receives ramucirumab IV on days 1 and 15 and paclitaxel IV on days 1, 8, and 15 of each cycle. Treatment continues every 28 days until disease progression or unacceptable side effects occur. Optional blood samples may be collected during the study. Imaging with CT and MRI is performed throughout. Participants undergo scans and assessments at baseline and during treatment to monitor cancer progression and treatment effects. They also complete questionnaires on quality of life and symptoms. After treatment ends, participants are followed up at 30, 60, and 90 days and then every 6 months for up to 3 years. Researchers measure progression-free survival and overall survival as primary outcomes, along with other safety and patient-reported measures.

Researchers are evaluating the addition of olaparib, a PARP inhibitor, as maintenance therapy following surgery and chemotherapy in patients with pancreatic cancer that has been surgically removed and who have a pathogenic mutation in BRCA1, BRCA2, or PALB2 genes. This phase II randomized, double-blind study aims to determine if olaparib can improve relapse-free survival compared to placebo in these patients, who have completed perioperative chemotherapy and have no evidence of recurrent disease. Participants are randomly assigned to receive either olaparib or a placebo orally twice daily in 28-day cycles for up to 12 cycles, as long as there is no disease progression or unacceptable side effects. Throughout the treatment period, patients undergo imaging tests such as CT scans or MRI and blood sample collections. After completing the treatment cycles, patients are followed up at 30 days, every 4 months for the first year, and then every 6 months for up to 10 years after randomization to monitor their health and disease status. During the study, researchers assess relapse-free survival by documenting any return of cancer or death from 22 to 44 months after randomization. They also collect blood samples and perform imaging tests to monitor the disease and evaluate treatment effects. Safety is carefully monitored, and patients must have recovered from previous treatments before starting the study. The study includes long-term follow-up to observe survival outcomes and any differences based on genetic mutations or prior chemotherapy regimens.

Researchers are evaluating the effect of adding chemotherapy to immunotherapy (pembrolizumab) compared to using immunotherapy alone in treating older adults aged 70 and above with advanced non-small cell lung cancer (stage IIIB-IV). This phase III trial aims to determine if combining chemotherapy with pembrolizumab improves overall survival and other outcomes like progression-free survival, response rates, toxicity, and quality of life in this vulnerable patient group. Participants are randomly assigned to one of two treatment groups. In the immunotherapy-alone group, patients receive pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years if there is no disease progression or unacceptable side effects. In the combination group, patients receive pembrolizumab plus a chemotherapy regimen chosen by their doctor, including drugs such as pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel, given intravenously on specific schedules for four cycles, followed by the same pembrolizumab maintenance. Imaging scans like MRI, CT, and PET are performed at baseline and throughout the study. During the study, participants undergo various assessments including imaging scans, laboratory tests, and questionnaires to evaluate treatment effects, side effects, and quality of life. Researchers monitor overall survival for up to five years from randomization, with follow-up visits every three months for the first two years and every six months thereafter until five years. Additional exploratory analyses include safety, tolerability, and correlations with gut microbiome and geriatric assessments to better understand treatment outcomes in this population.

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 three different combinations of drugs to treat newly diagnosed multiple myeloma in patients who are considered frail or intermediate-fit and are not eligible for stem cell transplant. This phase III trial focuses on comparing these three-drug induction treatments followed by either double- or single-drug maintenance therapy. The study aims to determine which treatment combination better controls the disease and improves progression-free survival and overall survival. Patients are randomly assigned to one of three treatment groups. Arm 1 (VRd-Lite) receives bortezomib by injection under the skin, lenalidomide by mouth, and dexamethasone by mouth during induction cycles, followed by lenalidomide alone for maintenance. Arm 2 (DRd-R) receives daratumumab and hyaluronidase-fihj injections, lenalidomide, and dexamethasone during induction, followed by lenalidomide alone during maintenance. Arm 3 (DRd-DR) receives the same induction as Arm 2, but maintenance includes both daratumumab and lenalidomide. Induction cycles last up to 9 cycles of 28 days each, and maintenance cycles continue every 28 days if the disease does not progress or toxicity occurs. Participants undergo assessments including tumor evaluations, whole-body imaging, blood tests, and quality-of-life questionnaires. After completing treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years. Researchers will measure progression-free survival, overall survival, response rates, safety, minimal residual disease, and patient-reported health outcomes to understand the treatments' effects and support future care decisions.

Researchers are evaluating the effectiveness of two different monoclonal antibody treatments, rituximab and mosunetuzumab, for patients with follicular lymphoma that has a low tumor burden. This is a phase III trial aiming to compare how well these treatments work in preventing disease progression, transformation to a more aggressive lymphoma, or death. The study also looks at overall survival, response rates, event-free survival, and the frequency and severity of side effects. Specimens will be collected and stored for future research. Participants are randomly assigned to one of two treatment groups. In the first group, patients receive rituximab intravenously on the first day and then rituximab combined with hyaluronidase subcutaneously on several days during a 56-day cycle, repeated for up to five cycles if the disease does not worsen or cause unacceptable side effects. In the second group, patients receive mosunetuzumab subcutaneously on several days during a 21-day cycle, repeated for up to eight cycles under the same conditions. Both groups undergo CT or PET/CT scans and blood sample collection during treatment and follow-up. After completing the treatment cycles, patients are followed every six months for five years and then yearly up to a total of 10 years to monitor their health and disease status. Researchers collect imaging results, blood tests, and other assessments to track progression-free survival, overall survival, treatment response, and safety. The study measures how long participants live without disease progression or transformation and records any treatment-related toxicities throughout the study period.

Researchers are evaluating whether breast conservation surgery combined with endocrine therapy can achieve a similar rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation surgery followed by breast radiation and endocrine therapy in patients with Stage I, hormone sensitive, HER2-negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial builds on the established role of radiation after lumpectomy, aiming to identify if radiation can be safely omitted in certain low-risk patients to reduce treatment burden and side effects. Participants receive either breast radiation plus endocrine therapy or endocrine therapy alone. Radiation therapy involves external beam radiation to the whole breast with or without a boost, partial breast irradiation, or accelerated partial breast irradiation, starting within 12 weeks after the last breast surgery. Endocrine therapy is given for a minimum of 5 years, with the specific drug choice and schedule determined by the treating physician. Endocrine therapy may begin before, during, or after radiation therapy, depending on the treatment group. Throughout the study, participants undergo regular assessments including imaging such as mammograms or MRI within six months before enrollment, and clinical evaluations to monitor tumor recurrence. The main outcome measured is the time to invasive or non-invasive ipsilateral breast tumor recurrence over five years. Safety, adherence to therapy, and recovery from surgery are also monitored. The total participation period includes at least five years to evaluate long-term recurrence rates.

Researchers are evaluating the incidence of colorectal cancer in people aged 45 to 70 who have 1 to 2 non-advanced adenomas, which are small precancerous polyps without high-risk features. The study compares outcomes between those who have surveillance colonoscopies every 5 years versus every 10 years. This is important because current guidelines recommend follow-up colonoscopy but lack clear evidence on the best timing for patients with non-advanced adenomas. Participants will undergo colonoscopies at either 5 and 10 years or just at 10 years after their initial qualifying colonoscopy. All colonoscopies, including any unscheduled ones, will follow standard quality procedures and preparation instructions. The initial colonoscopy must have fully visualized the cecum and completely removed all polyps. Sessile serrated polyps without advanced features are also included as non-advanced adenomas. During the trial, researchers will monitor participants through colonoscopy exams and collect data on the incidence of colorectal cancer over a 10-year period. The main measurement is the rate of colorectal cancer occurrence. The study also includes assessments to ensure adherence to colonoscopy quality standards and will follow participants long term to observe safety and effectiveness of the surveillance intervals.

Researchers are evaluating how factors like age, gender, other medical conditions, and the type of immunotherapy affect the development of side effects in patients with malignant solid tumors receiving immune checkpoint inhibitor (ICI) therapy. The study aims to develop and validate a risk prediction model for serious immune-related side effects during the first year of ICI treatment. Additional goals include tracking the occurrence of various side effects, quality of life, patient-reported symptoms, and treatment patterns over 12 months, along with studying biological markers that may predict side effect risk. Participants will have tissue samples collected at the start of their cancer treatment and will complete questionnaires at baseline and at weeks 4, 12, 24, and 52. Blood samples may also be collected at multiple times during the study. The study focuses on patients receiving standard-of-care ICI therapy for solid tumors, without combination chemotherapy or other non-ICI treatments. During the study, participants will complete patient-reported outcome forms and health questionnaires to assess side effects and quality of life. Researchers will monitor the occurrence of severe immune-related side effects over 52 weeks and evaluate biological markers from blood and tissue samples. The study also assesses the use of electronic methods for collecting patient data. Total participation includes assessments over approximately one year following treatment start.