This is an open-label, phase II study that may provide evidence that taking S-adenosylmethionine (SAMe) supplementation prevents oxaliplatin, a type of chemotherapy drug, associated liver toxicity in patients with resectable colorectal liver metastases. Resectable means that it is able to removed with surgery. Patients will take two SAMe tablets in the morning and one tablet in the evening for 3-6 months (about 6-8 cycles of chemotherapy) in addition to oxaliplatin based chemotherapy followed by surgical removal of the colorectal liver metastases.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
30
mFOLFOX6 or CAPOX
(400 mg tablet): 2 tablets taken orally AM and 1 tablet PM daily (total 1,200 mg daily) prior to surgical resection
At 1-Month
Cedars-Sinai Medical Center at SOCC
Los Angeles, California, United States
Cedars-Sinai Medical Center Beverly Hills
Los Angeles, California, United States
To evaluate the efficacy of SAMe in preventing oxaliplatin associated liver injury as determined by lack of injury on histopathologic analysis in patients with liver only stage IV colorectal cancer.
To identify the effect of SAMe in preventing oxaliplatin associated liver injury as determined by lack of injury on histopathologic analysis in patients with liver only stage IV colorectal cancer. Improvement in liver injury will be measured by the degree/histopathologic grade of liver injury utilizing the Combined Vascular Injury (CVI) Score in non-cancerous liver tissue post therapy compared to historical controls. CVI score will evaluate and grade sinusoidal dilation, small vessel loss/obliteration, focal hepatocyte plate disruption, parenchymal extinction lesions, nodular regenerative hyperplasia, peliosis, and veno-occlusive like changes. Rate of sinusoidal obstruction syndrome (SOS), as measured by CVI Score, ranging from 0-13. A CVI score of 3 or more indicates SOS. Compared to historical controls.
Time frame: 8 months
To Estimate the Objective Response Rate (ORR) of SAMe when taken with oxaliplatin based chemotherapy.
To evaluate the efficacy of SAMe during oxaliplatin based therapy in stage IV liver-only colorectal cancer, Objective Response Rate (ORR) will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) per RECIST 1.1. ORR will be assessed from screening until EOT.
Time frame: 8 months
To evaluate changes in average estimated blood loss (EBL) in patients undergoing liver resection as compared to historical controls.
Calculate surgical EBL in all patients undergoing resection
Time frame: 8 months
To evaluate length of hospital stay (LOS) in patients undergoing liver resection as compared to historical controls.
Length of hospital stay (LOS) to historical controls, the following will be conducted: ii. Calculate hospital LOS in all patients undergoing resection iii. Account for 30-day readmission
Time frame: 8 months
To examine if SAMe can decrease treatment-delays in oxaliplatin-based chemotherapy.
Incidence of oxaliplatin treatment delays will be evaluated by recording the following: If treatment delay occurred and time point/duration of treatment delay
Time frame: 8 months
To examine if SAMe can decrease dose-reductions in oxaliplatin-based chemotherapy.
Incidence of oxaliplatin dose reduction will be evaluated by recording the following: If dose reduction occurred and time point of occurrence
Time frame: 8 months
To evaluate safety and tolerability of SAMe in combination with SOC oxaliplatin based systemic therapy.
Safety and tolerability of the combination will be evaluated by determining the proportion of patients with treatment-related adverse events of all grades as graded per CTCAE v.5, from first dose of study drug until 30 days post last dose of study drug.
Time frame: 8 months
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