North Randall

This research aims to compare progression-free survival in adult participants with KRAS/NRAS and BRAF wild-type unresectable or metastatic left-sided colorectal cancer. The study evaluates two first-line treatment approaches: amivantamab combined with chemotherapy versus cetuximab combined with chemotherapy. This is a Phase 3 randomized, open-label trial assessing outcomes for this specific cancer type. Participants will be randomly assigned to one of two treatment groups. One group receives amivantamab along with chemotherapy cycles of either mFOLFOX6 (which includes 5-fluorouracil, leucovorin calcium or levoleucovorin, and oxaliplatin) or FOLFIRI (which includes 5-fluorouracil, leucovorin calcium or levoleucovorin, and irinotecan hydrochloride). The other group receives cetuximab combined with the same chemotherapy options. Each treatment cycle lasts 28 days, and participants continue treatment until disease progression or other stopping criteria are met. During the study, participants will undergo regular assessments including imaging scans reviewed by a blinded independent committee to measure progression-free survival up to 4 years and 2 months. Additional outcomes such as overall survival, response rates, duration of response, and quality of life will be monitored for up to over 7 years. Safety is tracked through adverse event reporting and laboratory tests. Participants' symptoms and functioning will also be evaluated using quality of life questionnaires throughout the study period.

Researchers are evaluating the anti-tumor activity and safety of amivantamab given as a subcutaneous co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) in participants with advanced or metastatic non-small cell lung cancer (NSCLC), including those with specific EGFR mutations. This Phase 2, open-label study includes multiple cohorts with different treatment histories and EGFR mutation types to better understand how amivantamab works in combination with other therapies and to assess its safety profile. Participants receive amivantamab subcutaneously at varying doses based on body weight and specific treatment cohorts. Some cohorts combine amivantamab with oral lazertinib or intravenous chemotherapy drugs such as carboplatin and pemetrexed, administered on different schedules ranging from every two to three weeks in 21- or 28-day cycles. Additional treatments like prophylactic anticoagulation may also be given in certain cohorts. Participants may have the option to enter a long-term extension phase to continue receiving study treatments. During the study, participants undergo regular evaluations including tumor assessments based on RECIST criteria and safety monitoring through adverse event tracking and laboratory tests. Researchers will measure objective response rates and other outcomes up to 1 year and 6 months, and for some cohorts, safety will be monitored for up to nearly 5 years. Participants' quality of life and treatment satisfaction are also assessed. The total duration of participation varies according to cohort and treatment response, with follow-up continuing after treatment completion.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer based on the presence or absence of circulating tumor DNA (ctDNA) after surgery. This Phase II/III trial focuses on patients with Stage IIB, IIC, or Stage III colon adenocarcinoma who have undergone tumor removal. The study aims to use ctDNA status to better predict the risk of cancer recurrence and guide decisions about adjuvant chemotherapy. Participants will be assigned to different treatment groups based on their ctDNA status after surgery. Patients without detectable ctDNA will undergo serial ctDNA monitoring without immediate treatment or receive standard chemotherapy regimens such as mFOLFOX6 or CAPOX for varying durations. Patients with detectable ctDNA will receive either standard chemotherapy or intensified regimens like mFOLFIRINOX. Treatments involve intravenous and oral chemotherapy drugs given over several cycles spanning weeks to months. Throughout the study, participants will have ctDNA testing using the Signatera test and be monitored for disease-free survival, overall survival, and recurrence up to five years after randomization. Safety and treatment adherence will also be tracked. Regular imaging and laboratory tests will assess disease status and organ function. The study may include re-randomization for patients who develop positive ctDNA during monitoring. Total involvement may last several years with follow-up for long-term outcomes.

Researchers are evaluating a treatment approach for early-stage hormone-sensitive, HER-2 negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial compares breast conservation surgery with endocrine therapy alone against breast conservation surgery with both radiation and endocrine therapy. The goal is to see if skipping radiation after lumpectomy is not worse in preventing cancer recurrence in the same breast. Participants will be randomly assigned to one of two groups. One group will receive radiation therapy to the breast plus at least five years of endocrine therapy with drugs such as Tamoxifen, Anastrozole, Letrozole, or Exemestane. The other group will receive endocrine therapy only for at least five years without radiation. Radiation must start within 12 weeks of surgery if assigned. Endocrine therapy dosing and schedule are determined by the treating doctor. During the study, participants will have regular follow-ups up to five years to monitor cancer recurrence in the breast and elsewhere, survival, and breast preservation. Assessments will include clinical exams, imaging like mammograms or MRI, and pathology reviews. The main outcome is time to invasive or noninvasive breast tumor recurrence within five years. Some measures will continue through an average of 15 years, including breast conservation rates. Safety and overall health will be monitored throughout and after treatment.

Researchers are evaluating whether adding the chemotherapy drug Docetaxel to the usual hormone treatments can better control metastatic castration sensitive prostate cancer (mCSPC) in patients who have not responded optimally to initial hormone therapy. This phase III randomized trial compares the combination of Docetaxel, Androgen Deprivation Therapy (ADT), and Androgen-Receptor Pathway Inhibitors (ARPI) to the usual treatment of ADT plus ARPI alone. The study focuses on men with a suboptimal PSA response after 6 to 12 months of androgen-targeting therapy. Participants will be randomly assigned to either continue with standard hormone therapy involving ADT and ARPI drugs such as abiraterone, enzalutamide, apalutamide, or darolutamide, or to receive Docetaxel chemotherapy added to this standard treatment. The treatments are given according to physician choice and prior assignment, with Docetaxel being introduced at enrollment for the experimental group. The study is open-label and conducted at multiple international centers. During the trial, participants will be monitored for overall survival over 39 months, along with PSA progression, PSA response, PSA kinetics, and clinical progression-free survival. Researchers will assess these outcomes to compare the two treatment approaches. Participants must be available for treatment and follow-up visits as scheduled, with regular testing of PSA levels, testosterone, organ function, and adverse event monitoring to ensure safety and evaluate treatment effects.

Researchers are evaluating whether adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival in premenopausal women with early-stage, estrogen receptor-positive, HER2-negative breast cancer. This Phase III trial focuses on patients with specific 21-gene recurrence scores and aims to clarify the best treatment approach for younger women, who face higher risks despite current therapies. The study addresses the uncertainty about the role of ovarian suppression combined with chemotherapy versus ovarian suppression alone in this patient group. Participants are randomly assigned to one of two treatment groups: one receiving ovarian function suppression with an aromatase inhibitor for 5 years, and the other receiving adjuvant chemotherapy followed by the same ovarian suppression and aromatase inhibitor regimen. The choice of drugs and dosing schedules for the aromatase inhibitor and GnRH agonist are determined by the investigators, with common options including monthly or every-three-months administration of agents like goserelin, leuprolide, or triptorelin. Endocrine therapy may continue beyond five years at the investigator’s discretion, and bilateral oophorectomy can substitute for ovarian suppression if preferred. Throughout the trial, participants will be closely monitored over 11 years for outcomes including invasive breast cancer-free survival, overall survival, distant recurrence-free interval, and breast cancer-free interval. Evaluations of menopausal symptoms and pain during aromatase inhibitor therapy will be conducted one year after randomization. The study involves regular assessments and follow-up to track the effectiveness and impact of the treatments on patients’ health and quality of life.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase II/III 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 combination of bevacizumab and osimertinib versus osimertinib alone as an initial treatment for patients with advanced non-small cell lung cancer (NSCLC) that has spread beyond the lungs and has specific mutations in the EGFR gene. This phase III trial aims to understand if adding bevacizumab, which inhibits blood vessel growth to tumors, can control cancer longer and improve survival compared to osimertinib alone, which blocks EGFR involved in tumor cell growth. Participants are randomly assigned to one of two groups. One group receives daily oral osimertinib every 21 days, while the other group receives the same osimertinib dose plus an intravenous bevacizumab infusion every 21 days. Treatment continues until disease progression or unacceptable side effects occur. During the study, patients undergo various imaging tests such as echocardiography, multigated acquisition scan, computed tomography, and possibly magnetic resonance imaging, along with blood and urine sample collections. After treatment ends, patients are followed every three months for up to 10 years to monitor their health and disease status. The main outcome measured is progression-free survival, tracking the time until the cancer worsens or death occurs. Secondary outcomes include overall survival, response rates, and effects on central nervous system progression. Safety is also assessed through adverse event monitoring. This long-term follow-up helps researchers understand the lasting effects of the treatments.

Researchers are evaluating patients with metastatic HER-2-positive breast cancer who are receiving trastuzumab-based therapy and are at risk of heart problems. The study includes two groups: one large observational group taking beta blockers, ACE inhibitors, or ARBs alongside trastuzumab, and a smaller randomized group comparing the effects of carvedilol versus no treatment. The aim is to understand the occurrence of heart issues and whether carvedilol might help prevent cardiac side effects from chemotherapy. Participants are assigned to one of three arms based on their current medications. Patients not on beta blockers, ARBs, or ACE inhibitors are randomized to either receive carvedilol orally twice daily or no study intervention. Those already taking these heart medications enter an observational arm without additional treatment. Treatment and observation continue for up to 108 weeks unless disease progression or unacceptable side effects occur. Throughout the study, participants undergo heart function monitoring with echocardiograms every 12 weeks and provide blood samples for biomarker analysis. Researchers track the time to the first sign of heart dysfunction and any cardiac events, as well as adherence to medication and side effects. The study also collects data to develop models predicting heart risk and banks samples for future research. Participant involvement may last over two years with regular assessments to monitor safety and heart health.

Researchers are evaluating how well serum tumor marker directed disease monitoring (STMDDM) works compared to usual care in patients with hormone receptor positive, HER2-negative metastatic breast cancer. This trial aims to see if monitoring with serum tumor markers can provide similar overall survival outcomes to the standard approach, which involves regular imaging scans. The study also looks at healthcare costs, patient anxiety, and quality of life related to these monitoring methods. Participants are randomly assigned to one of two groups. In the usual care group, patients receive imaging studies at least every 12 weeks and may have serum tumor marker tests as determined by their doctor. In the STMDDM group, patients have blood tests for specific tumor markers every 4 to 8 weeks, and imaging scans are only done if these markers indicate a possible progression of disease. Both groups continue their monitoring for up to 312 weeks unless the disease progresses. During the study, participants undergo regular assessments including blood tests for tumor markers, imaging scans as needed, and questionnaires about anxiety and quality of life. Researchers track overall survival for up to 312 weeks and compare healthcare costs and patient-reported outcomes for up to 48 to 102 weeks. The study also collects data on how often and by what methods disease monitoring is performed, along with patient and physician preferences related to monitoring.