This is a randomized, multi-center phase II study of ginseng in colorectal cancer patients treated with regorafenib to determine if ginseng will reduce fatigue in this patient population and improve adherence to regorafenib. Ninety (90) subjects will be enrolled and randomized using a 2:1 allocation, with 60 subjects enrolled in the regorafenib + ginseng group and 30 enrolled in the regorafenib + no ginseng group.
OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: Regorafenib will be administered 160 mg orally once daily for the first 21 days of each 28-day cycle. Subjects that randomize to receive ginseng will take 1,000 mg orally twice daily every day for 4 weeks (2 cycles). Subjects that randomize to NOT receive ginseng will not be given ginseng. Subjects will be instructed to take regorafenib with a low-fat meal. Subjects will undergo fatigue assessments, using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) instrument and Patient-Reported Outcomes Measurement Information System (PROMIS). Subjects will have a pill count cycle 2 day 1 (C2D1) and at the end of treatment visit. Subjects will have the re-staging scan (CT of chest/abdomen/pelvis) at the end of Cycle 2/ week 8 (±5). Adequate bone marrow, liver and renal function assessed by the following laboratory values obtained within 7 days prior to registration for protocol therapy: Hematopoietic: * Absolute neutrophil count (ANC) count \> 1,500/mm\^3 * Hemoglobin (Hgb) \> 9g/dL * Platelet count \> 100,000/mm\^3 Renal: * Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) Hepatic: * Total bilirubin ≤ 1.5 × the upper limit of normal (ULN). * Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 × ULN for subjects with liver involvement of their cancer) * Alkaline phosphatase (ALP) limit ≤ 2.5 × ULN (≤ 5 × ULN for subjects with liver involvement of their cancer) Coagulation: * International normalized ratio (INR)/Partial thromboplastin time (PTT) ≤ 1.5 × ULN. NOTE: Subjects who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable, based on a measurement that is pre-dose as defined by the local standard of care. Warfarin does should not exceed 1 mg.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.
Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Indiana Univeristy Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Altantic Health System
Morristown, New Jersey, United States
Comprehensive Cancer Center at Wake Forest Baptist
Winston-Salem, North Carolina, United States
Subject Fatigue Assessment--Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)
MFSI-SF is a 30-item self-report instrument designed to measure general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigor--each scored on a 5-point Likert scale from 0 ("not at all") to 4 ("extremely"). The total score is calculated by adding the general, physical, emotional, and mental subscale scores and subtracting the vigor subscale score. Thus, total scores can range from -24 to 96 where higher scores indicate more of the cancer-related fatigue (meaning higher scores represent worse fatigue). A minimally clinically important improvement (or worsening) in the MFSI-Short Form is for changes of more than 4.5 points. T-score value of 36 indicates the population mean with a standard deviation of 34.93.
Time frame: From date of first dose until end of cycle 2 (8 weeks)
Subject Fatigue Assessment--Patient-Reported Outcomes Measurement Information System (PROMIS)
PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Each of the total raw scores were translated into T-scores for each participant using scoring tables for converting the PROMIS short form. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person with a T-score of 40 is one SD below the mean. A higher PROMIS T-score represents more of the concept being measured. For this instrument all questions were negatively worded (i.e., How fatigued were you on average?) therefore a higher T-score represents having more fatigue. Thus, a T-score of 60 is one SD
Time frame: From date of first dose until end of cycle 2 (8 weeks)
Subject Compliance
Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.
Time frame: Cycle 1 From date of first dose until day 15
Subject Compliance
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Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States
Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.
Time frame: Cycle 2 From date of first dose until day 15
Subject Compliance
Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.
Time frame: Cycle 1 From day16 until day 22
Subject Compliance
Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.
Time frame: Cycle 2 From day 16 until day 22
Characterize Adverse Events (AE)
Toxicity assessed using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0) criteria
Time frame: From date of first dose until end of cycle 2 (8 weeks)
Subject Retention
Retention will be determined by the proportion of subjects on each arm who complete the study.
Time frame: From date of first dose until end of cycle 2 (8 weeks)
Evaluate Response Rate (RR)
the number of subjects with confirmed partial response (PR) or complete response (CR) according to RECIST v.1.1, from the start of treatment until disease progression/recurrence
Time frame: From cycle 1 day 1 (C1D1) until death or up to 18 months
Number of Participants With Overall Survival
date of randomization to date of death from any cause
Time frame: From C1D1 until death or up to 18 months