Trial Outcomes & Findings for Efficacy of Ginseng for Patients on Regorafenib (NCT NCT02581059)

Last Updated: 2024-06-26

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

From date of first dose until end of cycle 2 (8 weeks)

Results posted on

2024-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Regorafenib Only Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Study Treatment STARTED	4	6
Study Treatment COMPLETED	0	1
Study Treatment NOT COMPLETED	4	5
Follow up STARTED	3	5
Follow up COMPLETED	0	0
Follow up NOT COMPLETED	3	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Regorafenib Only Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Study Treatment Disease Progression	1	1
Study Treatment Adverse Event	2	1
Study Treatment Death	1	1
Study Treatment Patient Withdrawal After Therapy Start	0	1
Study Treatment Screen Failure Before Therapy Start	0	1
Follow up Death	1	3
Follow up study terminated	1	1
Follow up screen failure	0	1
Follow up Patient started new clinical trial	1	0

Baseline Characteristics

Efficacy of Ginseng for Patients on Regorafenib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regorafenib Only n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Non-Hispanic	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) status 0	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) status 1	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of first dose until end of cycle 2 (8 weeks)

Population: Data not collected for one in each group.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=3 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Fatigue Assessment--Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)	5.33 score on a scale Standard Deviation 8.39	8.50 score on a scale Standard Deviation 23.84	—

PRIMARY outcome

Timeframe: From date of first dose until end of cycle 2 (8 weeks)

Population: Data not collected from one participant in each group.

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

Outcome measures

Outcome measures
Measure	Regorafenib Only n=3 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Fatigue Assessment--Patient-Reported Outcomes Measurement Information System (PROMIS)	18 T-Score Standard Deviation 6.24	22.75 T-Score Standard Deviation 11.64	—

SECONDARY outcome

Timeframe: Cycle 1 From date of first dose until day 15

Population: Data not collected from missing participants in each group/arm.

Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) n=1 Participants Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Compliance	100 percentage of pills taken	—	75 percentage of pills taken

SECONDARY outcome

Timeframe: Cycle 2 From date of first dose until day 15

Population: Data was not collected from missing participants in each group/arm.

Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) n=2 Participants Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Compliance	75 percentage of pills taken	100 percentage of pills taken	100 percentage of pills taken Standard Deviation 50

SECONDARY outcome

Timeframe: Cycle 1 From day16 until day 22

Population: Data was not collected from missing participants in each group/arm.

Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) n=1 Participants Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Compliance	100 percentage of pills taken	75 percentage of pills taken	100 percentage of pills taken

SECONDARY outcome

Timeframe: Cycle 2 From day 16 until day 22

Population: Data was not collected from missing participants in each group/arm.

Pill counts will be used to assess adherence to regorafenib and ginseng for subjects on each arm. Overall percentage reported.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) n=1 Participants Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Compliance	75 percentage of pills taken	—	50 percentage of pills taken

SECONDARY outcome

Timeframe: From date of first dose until end of cycle 2 (8 weeks)

Toxicity assessed using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0) criteria

Outcome measures

Outcome measures
Measure	Regorafenib Only n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Characterize Adverse Events (AE) Acute Kidney Injury	0 Participants	1 Participants	—
Characterize Adverse Events (AE) ALANINE AMINOTRANSFERASE INCREASED	0 Participants	1 Participants	—
Characterize Adverse Events (AE) HEPATOBILIARY DISORDERS	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From date of first dose until end of cycle 2 (8 weeks)

Retention will be determined by the proportion of subjects on each arm who complete the study.

Outcome measures

Outcome measures
Measure	Regorafenib Only n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Subject Retention Started	4 Participants	6 Participants	—
Subject Retention Completed (total retained number)	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From cycle 1 day 1 (C1D1) until death or up to 18 months

Population: Data not collected for this outcome from missing participants in each arm.

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

Outcome measures

Outcome measures
Measure	Regorafenib Only n=1 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=2 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Evaluate Response Rate (RR)	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From C1D1 until death or up to 18 months

date of randomization to date of death from any cause

Outcome measures

Outcome measures
Measure	Regorafenib Only n=4 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 Participants Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng Arm (Ginseng Compliance Only) Ginseng compliance for Regorafenib + Ginseng arm Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Number of Participants With Overall Survival	2 Participants	2 Participants	—

Adverse Events

Regorafenib Only

Serious events: 0 serious events

Other events: 4 other events

Deaths: 2 deaths

Regorafenib + Ginseng

Serious events: 2 serious events

Other events: 5 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Regorafenib Only n=4 participants at risk Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 participants at risk Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Renal and urinary disorders ACUTE KIDNEY INJURY	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Hepatobiliary disorders HEPATOBILIARY DISORDERS	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.

Other adverse events

Additional Information

Annesha Majumdar

Hoosier Cancer Research Network

Phone: 3179212050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Regorafenib Only n=4 participants at risk Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle for 2 cycles. Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles.	Regorafenib + Ginseng n=6 participants at risk Regorafenib will be administered 160 mg once daily for the first 21 days of each 28-day cycle. Subjects will receive 1,000 mg ginseng orally twice daily every day for 4 weeks (2 cycles). Regorafenib: All subjects will receive regorafenib 160 mg orally once daily for the first 21 days of each 28-day cycle for 2 cycles. Ginseng: Subjects randomized to ginseng will receive 1,000 mg orally twice every day of each 28-day cycle for 2 cycles.
Gastrointestinal disorders ABDOMINAL PAIN	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations ALKALINE PHOSPHATASE INCREASED	50.0% 2/4 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders ANOREXIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	50.0% 3/6 • Number of events 6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations BLOOD BILIRUBIN INCREASED	50.0% 2/4 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	66.7% 4/6 • Number of events 6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Musculoskeletal and connective tissue disorders BONE PAIN	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
General disorders CHILLS	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders CONSTIPATION	50.0% 2/4 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders COUGH	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders DYSPNEA	25.0% 1/4 • Number of events 4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
General disorders EDEMA LIMBS	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
General disorders FATIGUE	75.0% 3/4 • Number of events 7 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	66.7% 4/6 • Number of events 9 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Musculoskeletal and connective tissue disorders GENERALIZED MUSCLE WEAKNESS	50.0% 2/4 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Renal and urinary disorders HEMATURIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders HOARSENESS	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPOALBUMINEMIA	50.0% 2/4 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPOCALCEMIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPOGLYCEMIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPOKALEMIA	25.0% 1/4 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 5 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPONATREMIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations LYMPHOCYTE COUNT DECREASED	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
General disorders MALAISE	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders NAUSEA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Cardiac disorders PERICARDIAL EFFUSION	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	50.0% 2/4 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations PLATELET COUNT DECREASED	50.0% 2/4 • Number of events 6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Infections and infestations RASH PUSTULAR	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Cardiac disorders SINUS TACHYCARDIA	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Skin and subcutaneous tissue disorders SKIN ULCERATION	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Infections and infestations UPPER RESPIRATORY INFECTION	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	0.00% 0/6 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders VOMITING	25.0% 1/4 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations WEIGHT LOSS	75.0% 3/4 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	50.0% 3/6 • Number of events 5 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Blood and lymphatic system disorders ANEMIA	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Psychiatric disorders ANXIETY	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	50.0% 3/6 • Number of events 9 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Eye disorders BLURRED VISION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Reproductive system and breast disorders BREAST PAIN	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Renal and urinary disorders CHRONIC KIDNEY DISEASE	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Psychiatric disorders CONFUSION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations CREATININE INCREASED	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Psychiatric disorders DEPRESSION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders DIARRHEA	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	50.0% 3/6 • Number of events 5 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders DRY MOUTH	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders DYSPHAGIA	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Nervous system disorders HEADACHE	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders HEMORRHOIDS	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Vascular disorders HYPERTENSION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	33.3% 2/6 • Number of events 2 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Vascular disorders HYPOTENSION	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders MUCOSITIS ORAL	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders ORAL PAIN	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Reproductive system and breast disorders PELVIC PAIN	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Gastrointestinal disorders RECTAL PAIN	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders SORE THROAT	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 3 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.
Investigations WHITE BLOOD CELL DECREASED	0.00% 0/4 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.	16.7% 1/6 • Number of events 1 • Begin C1D1 and every chemotherapy cycles (4 weeks) thereafter, for up to 18 months or until unacceptable toxicity.