Trial Outcomes & Findings for Trial of Trientine Plus Pegylated Liposomal Doxorubicin and Carboplatin in Epithelial Ovarian Cancer (NCT NCT03480750)

Last Updated: 2020-11-10

Results Overview

(1) Grade 4 neutropenia (ANC \<500/cumm\^3) or thrombocytopenia ≧7 days; (2) Hematologic toxicities ≧ Grade 3, eg. febrile neutropenia \<1,000/cumm\^3, or platelet count \<25,000/cumm\^3 with hemorrhage ≧ 7 days; (3) Non-hematologic toxicities ≧ grade 3, eg. ALT or AST, ≧ 7days; other non-hematologic toxicities ≧ grade 3 (except alopecia, non-chemotherapy related nausea/vomiting); (4) Neurologic toxicities ≧ grade 2, eg. dizziness, or lethargy ≧ 3 days

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

36 days

Results posted on

2020-11-10

Participant Flow

Between September 1, 2012 and October 30, 2015, eligible patients were enrolled in a medical center, National Cheng Kung University Hospital.

Participant milestones

Participant milestones
Measure	Trientine With Chemotherapy Dose Level 1 (300mg) trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 2 (600mg) trientine dihydrochloride: trientine dihydrochloride 600MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 3 (900mg) trientine dihydrochloride: trientine dihydrochloride 900MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 4 (1200mg) trientine dihydrochloride: trientine dihydrochloride 1200MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg) trientine dihydrochloride: trientine dihydrochloride 1500MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg) trientine dihydrochloride: trientine dihydrochloride 1800MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Overall Study STARTED	3	4	3	3	3	2
Overall Study COMPLETED	3	3	3	3	3	1
Overall Study NOT COMPLETED	0	1	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Trientine With Chemotherapy Dose Level 1 (300mg) trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 2 (600mg) trientine dihydrochloride: trientine dihydrochloride 600MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 3 (900mg) trientine dihydrochloride: trientine dihydrochloride 900MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 4 (1200mg) trientine dihydrochloride: trientine dihydrochloride 1200MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg) trientine dihydrochloride: trientine dihydrochloride 1500MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg) trientine dihydrochloride: trientine dihydrochloride 1800MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Overall Study Withdrawal by Subject	0	1	0	0	0	0
Overall Study The interruption in Trientine shippment	0	0	0	0	0	1

Baseline Characteristics

Trial of Trientine Plus Pegylated Liposomal Doxorubicin and Carboplatin in Epithelial Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trientine With Chemotherapy Dose Level 1 (300mg) n=3 Participants trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 2 (600mg) n=4 Participants trientine dihydrochloride: trientine dihydrochloride 600MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 3 (900mg) n=3 Participants trientine dihydrochloride: trientine dihydrochloride 900MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 4 (1200mg) n=3 Participants trientine dihydrochloride: trientine dihydrochloride 1200MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg) n=3 Participants trientine dihydrochloride: trientine dihydrochloride 1500MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg) n=2 Participants trientine dihydrochloride: trientine dihydrochloride 1800MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Total n=18 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	15 Participants n=8 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	3 Participants n=8 Participants
Age, Continuous	60.3 years n=5 Participants	56.3 years n=7 Participants	63.7 years n=5 Participants	50.7 years n=4 Participants	47 years n=21 Participants	56 years n=8 Participants	55.7 years n=8 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	18 Participants n=8 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	18 Participants n=8 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Region of Enrollment Taiwan	3 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	2 participants n=8 Participants	18 participants n=8 Participants
Interval from the end of primary chemotherapy < 6 months	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	7 Participants n=8 Participants
Interval from the end of primary chemotherapy 6-12 months	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	11 Participants n=8 Participants
Histology Serous adenocarcinoma	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	10 Participants n=8 Participants
Histology Clear cell carcinoma	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	4 Participants n=8 Participants
Histology Mucinous adenocarcinoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants
Histology Mixed serous and clear cell carcinoma	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Histology Mixed endometrioid and clear cell carcinoma	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants

PRIMARY outcome

Timeframe: 36 days

Population: One participant receiving 600 mg/day declined the trial drugs and did not proceed with treatment.Therefore, an additional participant was included at the same dose level.

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) n=3 Participants rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) n=2 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Number of Participants With Dose-Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: within 36 days after the start of Trientine

Population: One participant receiving 600 mg/day declined the trial drugs and did not proceed with treatment.Therefore, an additional participant was included at the same dose level.

'3+3' study design. MTD will be defined at the dose level of trientine prior to the level with DLT events ≧ 2/6 participants.

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=17 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Maximum Tolerated Dose, MTD	NA mg No DLTs or treatment-related deaths were reported, which may be due to insufficient number of participants with events to determine MTD.	—	—	—	—	—

SECONDARY outcome

Timeframe: 0, 10mins, 30mins, 60mins, 90mins, 120mins, 4h, 6h, 24h, 148h, 150h, 153h, 156h post 1st dose of trientine

Trientine (TETA) prior to and within 24 hrs and 7 days after trientine

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) n=3 Participants rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) n=3 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) n=2 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Maximum Plasma Concentration [Cmax] of Trientine	1.87 mg/L Interval 1.01 to 2.73	5.07 mg/L Interval 0.83 to 9.31	11.54 mg/L Interval 3.31 to 19.76	14.98 mg/L Interval 8.95 to 21.01	13.08 mg/L Interval 0.0 to 27.1	29.35 mg/L Interval 0.0 to 29.35

SECONDARY outcome

Timeframe: 36 months

Population: According the protocol for this secondary outcome, data collected from participants receiving different dose levels were intended to be combined and analyzed as a single group.

Time is calculated from the diagnosis to the last follow-up date if no disease progression , or the date of disease progression after the last treatment cycle of the study drugs

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=16 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Progression-free Survival	4.6 months Interval 0.0 to 11.3	—	—	—	—	—

SECONDARY outcome

Timeframe: 36 months

Population: According the protocol for this secondary outcome, data collected from participants receiving different dose levels were intended to be combined and analyzed as a single group

Time is calculated from the diagnosis to the date of the last follow-up date if no death event, or the date of death.

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=16 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Overall Survival	14.4 months Interval 0.0 to 34.2	—	—	—	—	—

SECONDARY outcome

Timeframe: 176 days

Population: Two participants who declined any of the study agents after enrollment or declined the initial chemotherapy drug after a 7-day course of trientine were deemed ineligible for this analysis. According the protocol for this secondary outcome, all participants were not described separately.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan

Outcome measures

Outcome measures
Measure	Trientine With Chemotherapy at Dose Level 1 (300mg/d) n=16 Participants trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 1st dose level: 300mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 2 (600mg/d) rientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 2nd dose level: 600mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy at Dose Level 3 (900mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 3rd dose level: 900mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1	Trientine With Chemotherapy at Dose Level 4 (1200mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 4th dose level: 1200mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 5th dose level: 1500mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg/d) trientine dihydrochloride PO daily plus pegylated liposomal doxorubicin IV D1 plus carboplatin IV D1 trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily (at 6th dose level: 1800mg) pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1 Clinical benefit rates	43.8 percentage of participants	—	—	—	—	—
Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1 Response rates	25.0 percentage of participants	—	—	—	—	—

Adverse Events

Trientine With Chemotherapy Dose Level 1 (300mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Trientine With Chemotherapy Dose Level 2 (600mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Trientine With Chemotherapy Dose Level 3 (900mg)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Trientine With Chemotherapy Dose Level 4 (1200mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Trientine With Chemotherapy Dose Level 5 (1500mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Trientine With Chemotherapy Dose Level 6 (1800mg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Trientine With Chemotherapy Dose Level 1 (300mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 2 (600mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 600MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 3 (900mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 900MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 4 (1200mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 1200MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 1500MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg) n=2 participants at risk trientine dihydrochloride: trientine dihydrochloride 1800MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.

Other adverse events

Other adverse events
Measure	Trientine With Chemotherapy Dose Level 1 (300mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 300MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 2 (600mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 600MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 3 (900mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 900MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 4 (1200mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 1200MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 5 (1500mg) n=3 participants at risk trientine dihydrochloride: trientine dihydrochloride 1500MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1	Trientine With Chemotherapy Dose Level 6 (1800mg) n=2 participants at risk trientine dihydrochloride: trientine dihydrochloride 1800MG/CAPSUE PO daily pegylated liposomal doxorubicin: pegylated liposomal doxorubicin 40mg/m2 IV D1 carboplatin: carboplatin AUC 4 IV D1
Investigations Leukopenia	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Investigations Neutrophil count decreased	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Blood and lymphatic system disorders Anemia	100.0% 3/3 • Number of events 5 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 6 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 5 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 5 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 2/2 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Investigations Thrombocytopenia	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Gastrointestinal disorders Vomiting	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Gastrointestinal disorders Mucositis	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Nervous system disorders Paresthesia	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Nervous system disorders Dizziness	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
General disorders Fatigue	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 5 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 5 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 2/2 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Skin and subcutaneous tissue disorders Hand-foot syndrome	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Skin and subcutaneous tissue disorders Skin rash	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 4 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 2/2 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
General disorders Fever	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Investigations Aspartate aminotransferase increased	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	66.7% 2/3 • Number of events 2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	50.0% 1/2 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Investigations Alanine aminotransferase increased	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.
Investigations Alkaline phosphatase increased	100.0% 3/3 • Number of events 3 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	33.3% 1/3 • Number of events 1 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.	0.00% 0/2 • All-Cause Mortality was assessed up to 36 months and Serious and Other (non-serious) Adverse Events were assessed within the planned 6-month treatment duration Adverse event severity was graded according to the Common Terminology Criteria for Adverse Events, version 4.03. All participants who received at least one dose of any of the study agents were considered evaluable for safety.

Additional Information

Dr. Yu-Fang Huang

National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University

Phone: 886 6 2353535

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place