The goal of this clinical trial is to learn if adding amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) to Fruquintinib in metastatic colorectal cancer that has not responded to other standard treatment is:
* Effective in improving survival * safe and tolerable
Participant must have histologically or cytologically confirmed metastatic colorectal adenocarcinoma. There must be previous documentation of RAS (Rat sarcoma mutation), BRAF (B-Raf proto-oncogene, Serine/threonine kinase), MSI/MMR (microsatellite instability, mismatch repair) , and HER2 (Human epidermal growth factor receptor 2) status.
Fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy
Anti-VEGF (vascular endothelial growth factor) biological therapy, such as bevacizumab, aflibercept, or ramucirumab
If RAS is wild type, an anti-EGFR (epidermal growth factor receptor) therapy like cetuximab or panitumumab
Participants with uncontrolled hypertension per investigator discretion.
Participants with a history or presence of gastric/duodenal ulcer or ulcerative colitis, hemorrhage of an unresected gastrointestinal tumor, perforation, fistulas, or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation.
Participants with a history or presence of hemorrhage from any other site (i.e., lower GI bleed, hemoptysis or hematemesis) within two months prior to screening.
Participants with a history of a thromboembolic event, including deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial embolism within three months prior to screening unless they are on a stable dose of anticoagulant and no further evidence of active thromboses are seen on CT scan or venous Doppler imaging. Participants with saddle (massive) pulmonary embolism that require thrombectomy/thrombolysis within 12 months of screening are excluded from the trial.
Single group
Fruquintinib
DrugFruquintinib is a small molecule tyrosine kinase inhibitor (TKI) that targets VEGFR-1, -2, and -3, with a novel chemical structure which belongs to the quinazoline class
TheraBionic P1
DeviceTheraBionic P1 is a amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) device
Overall Survival (OS)
Overall survival (OS) is defined as the time duration from treatment start until death of any cause. The distribution of OS will be graphically summarized by a Kaplan-Meier (KM) curve, and median OS (mOS) and its one-sided 85% (i.e., two-sided 70%) confidence interval (CI) will be estimated using KM estimates.
Safety and Tolerability
Analyses will be performed for all participants who have received fruquintinib and TheraBionic P1 treatment. AEs will be graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Adverse Events will be summarized by count and frequency. Corresponding two-sided 95% CI will be calculated using Clopper and Pearson's method.
Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time duration from treatment start to progression or death of any cause. Progression of disease will be assessed and determined by the treating investigator. A one-sample log-rank test will be performed to evaluate PFS. The distribution of PFS will be graphically summarized by Kaplan-Meier (KM) curve and median PFS (mPFS) and its 95% CI will be estimated using KM estimates.
Rates of progressive disease
The proportions of participants whose disease has progressed after treatment initiation will be computed by dividing the number of participants with progression by the total number of patients who were followed.
Changes in serum Carcinoembryonic Antigen (CEA)
Serum CEA will be measured at baseline, on Day 1 of each cycle, and at the end of treatment. Distribution of levels of serum CEA will be checked and, if needed, data transformation will be employed for normality. The levels of serum CEA will be descriptively summarized using mean, median, standard deviation (SD), range, and 95% CI per each time point. The changes in serum CEA will be also descriptively summarized using the same descriptive statistics. The associations between the change of serum CEA and each of efficacy outcomes will be descriptively evaluated using logistic and Cox proportional hazard regression models. The proportional hazard assumption will be checked and, if violated, a weighed Cox regression model or restricted mean survival time will be utilized.
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Barbara Ann Karmanos Cancer Institute
Lead sponsor
THERABIONIC INC.
Collaborator
