Trial Outcomes & Findings for Pazopanib Hydrochloride With or Without Ascorbic Acid in Treating Patients With Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery (NCT NCT03334409)

Last Updated: 2022-03-31

Results Overview

Treatment failure is defined as any of the following: radiographic disease progression, off-protocol treatment due to adverse event, initiation of alternative therapy (except metastasectomy post clinical benefit (complete response \[CR\], partial response \[PR\], or stable disease \[SD\] per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 to treatment), and death due to any cause.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

At 40 weeks

Results posted on

2022-03-31

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	2	3
Overall Study COMPLETED	1	3
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Overall Study Did not meet inclusion criteria	1	0

Baseline Characteristics

Pazopanib Hydrochloride With or Without Ascorbic Acid in Treating Patients With Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Total n=4 Participants Total of all reporting groups
Age, Continuous	55 years n=93 Participants	56.7 years n=4 Participants	56.3 years n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
MSKCC Risk Factor Poor risk	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
MSKCC Risk Factor Intermediate risk	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
MSKCC Risk Factor Favorable risk	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: At 40 weeks

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Treatment Failure-free Rate	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 26 months

Will be estimated using the method of Kaplan-Meier and be compared using log rank tests.

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Overall Survival	7.8 Months Too few patients to calculate.	NA Months No events occurred, the lower limit, median, and upper limit were not reached.

SECONDARY outcome

Timeframe: 16 Months

Will be estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Progression Free Survival	5.7 Months Interval 5.7 to 5.7	11.8 Months Interval 7.3 to 15.9

SECONDARY outcome

Timeframe: 16 Months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan, PET/CT, or MRI: Complete Response (CR), Disappearance of all target lesions and all target lymph nodes must have reduction in short axis to \<1.0 cm; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation; Overall Response (OR) = CR + PR. Will be compared using a Chi-Square test.

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Overall Response Rate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 10 months

Will be described as the median time on treatment by arm.

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Duration of Time on Pazopanib Hydrochloride	5.9 Months Interval 5.9 to 5.9	9.2 Months Interval 7.3 to 9.2

SECONDARY outcome

Timeframe: 10 Months

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events and toxicities will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event frequencies for grade 3 or higher adverse events, will be compared using Chi-Square tests between the 2 treatment arms.

Outcome measures

Outcome measures
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 Participants Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Frequency of Adverse Events	1 Participants	2 Participants

Adverse Events

Arm A (Pazopanib Hydrochloride, Ascorbic Acid)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Arm B (Pazopanib Hydrochloride)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 participants at risk Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 participants at risk Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Infections and infestations Lung infection	100.0% 1/1 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	0.00% 0/3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Injury, poisoning and procedural complications Fracture	100.0% 1/1 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	0.00% 0/3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Alanine aminotransferase increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Respiratory, thoracic and mediastinal disorders Hypoxia	100.0% 1/1 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	0.00% 0/3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Vascular disorders Thromboembolic event	100.0% 1/1 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	0.00% 0/3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months

Other adverse events

Additional Information

Lance Pagliaro, M.D.

Mayo Clinic, Rochester

Phone: (507)293-0566

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A (Pazopanib Hydrochloride, Ascorbic Acid) n=1 participants at risk Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Pazopanib Hydrochloride) n=3 participants at risk Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Endocrine disorders Hypothyroidism	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Eye disorders Dry eye	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Eye disorders Eye disorders - Other, specify	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Anal fistula	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Diarrhea	100.0% 1/1 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	100.0% 3/3 • Number of events 19 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Dry mouth	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Dyspepsia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Dysphagia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Flatulence	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Mucositis oral	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	66.7% 2/3 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 4 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	100.0% 3/3 • Number of events 15 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
General disorders Fatigue	100.0% 1/1 • Number of events 6 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	100.0% 3/3 • Number of events 26 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
General disorders Gen disord and admin site conds-Oth spec	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
General disorders Pain	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 4 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Infections and infestations Urinary tract infection	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Alanine aminotransferase increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	66.7% 2/3 • Number of events 5 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Aspartate aminotransferase increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	66.7% 2/3 • Number of events 5 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Blood bilirubin increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Creatinine increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	66.7% 2/3 • Number of events 15 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations GGT increased	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Investigations Weight loss	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 8 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Metabolism and nutrition disorders Dehydration	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Metabolism and nutrition disorders Hyponatremia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Nervous system disorders Dysgeusia	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 8 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Nervous system disorders Headache	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Nervous system disorders Nervous system disorders - Oth spec	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Nervous system disorders Peripheral sensory neuropathy	100.0% 1/1 • Number of events 5 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Psychiatric disorders Anxiety	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Psychiatric disorders Depression	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Reproductive system and breast disorders Vaginal dryness	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrm	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 4 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Skin and subcutaneous tissue disorders Skin and subcut tissue disord - Oth spec	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Social circumstances Social circumstances - Other, specify	0.00% 0/1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	33.3% 1/3 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Vascular disorders Hypertension	100.0% 1/1 • Number of events 4 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months	100.0% 3/3 • Number of events 24 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months