Trial Outcomes & Findings for Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors (NCT NCT04234568)

Last Updated: 2025-12-22

Results Overview

The MTD and RP2D will be estimated using isotonic regression based on observed dose limiting toxicity from all patients enrolled in the phase 1 portion and expansion cohort. All patients who received study drugs will be included in the safety analysis.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

8 weeks (56 days)

Results posted on

2025-12-22

Participant Flow

Two participants were consented and enrolled to the study but were subsequently discovered to be screen failures. They did not receive study treatment or get assigned to an arm.

Participant milestones

Participant milestones
Measure	Escalation Phase Dose Level 1 (100mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 2 (150mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Overall Study STARTED	3	11	1	2	14
Overall Study COMPLETED	3	11	1	2	14
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Escalation Phase Dose Level 1 (100mg Triapine) n=3 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 2 (150mg Triapine) n=11 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) n=1 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) n=2 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) n=14 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	0 Participants n=127 Participants	0 Participants n=77 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=18 Participants	10 Participants n=102 Participants	0 Participants n=30 Participants	1 Participants n=37 Participants	11 Participants n=127 Participants	24 Participants n=77 Participants
Age, Categorical >=65 years	1 Participants n=18 Participants	1 Participants n=102 Participants	1 Participants n=30 Participants	1 Participants n=37 Participants	3 Participants n=127 Participants	7 Participants n=77 Participants
Sex: Female, Male Female	1 Participants n=18 Participants	2 Participants n=102 Participants	0 Participants n=30 Participants	1 Participants n=37 Participants	9 Participants n=127 Participants	13 Participants n=77 Participants
Sex: Female, Male Male	2 Participants n=18 Participants	9 Participants n=102 Participants	1 Participants n=30 Participants	1 Participants n=37 Participants	5 Participants n=127 Participants	18 Participants n=77 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	1 Participants n=127 Participants	1 Participants n=77 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=18 Participants	11 Participants n=102 Participants	1 Participants n=30 Participants	2 Participants n=37 Participants	12 Participants n=127 Participants	29 Participants n=77 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	1 Participants n=127 Participants	1 Participants n=77 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	0 Participants n=127 Participants	0 Participants n=77 Participants
Race (NIH/OMB) Asian	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	0 Participants n=127 Participants	0 Participants n=77 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	0 Participants n=127 Participants	0 Participants n=77 Participants
Race (NIH/OMB) Black or African American	0 Participants n=18 Participants	1 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	1 Participants n=127 Participants	2 Participants n=77 Participants
Race (NIH/OMB) White	3 Participants n=18 Participants	10 Participants n=102 Participants	1 Participants n=30 Participants	2 Participants n=37 Participants	12 Participants n=127 Participants	28 Participants n=77 Participants
Race (NIH/OMB) More than one race	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	0 Participants n=127 Participants	0 Participants n=77 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	1 Participants n=127 Participants	1 Participants n=77 Participants
Region of Enrollment United States	3 participants n=18 Participants	11 participants n=102 Participants	1 participants n=30 Participants	2 participants n=37 Participants	14 participants n=127 Participants	31 participants n=77 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	2 Participants n=18 Participants	9 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants	10 Participants n=127 Participants	21 Participants n=77 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	1 Participants n=18 Participants	2 Participants n=102 Participants	1 Participants n=30 Participants	2 Participants n=37 Participants	4 Participants n=127 Participants	10 Participants n=77 Participants

PRIMARY outcome

Timeframe: 8 weeks (56 days)

Population: One patient in the expansion phase was not evaluable for dose limiting toxicity or for MTD determination

Outcome measures

Outcome measures
Measure	Escalation Phase n=15 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase n=15 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Maximum Tolerated Dose (MTD) of Triapine and Recommended Phase 2 Dose (RP2D)	150 milligrams	150 milligrams	—	—	—

PRIMARY outcome

Timeframe: 8 weeks (56 days)

Population: One patient from the expansion phase was not evaluable for DLTs.

DLTs will be summarized descriptively at each dose level. Will be summarized based on Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of toxicity for each adverse event category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will describe all serious (\>= grade 3) toxicity events on a patient-by-patient basis. Frequency and incidence tables of toxicity and adverse events will be generated in the overall patient group and by dose level depending on patient enrollment.

Outcome measures

Outcome measures
Measure	Escalation Phase n=3 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase n=11 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) n=2 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) n=13 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) n=1 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Dose Limiting Toxicity (DLT) Grade 5 Cardiac Arrest	0 participants	0 participants	0 participants	0 participants	1 participants
Dose Limiting Toxicity (DLT) Grade 4 Neutropenia	0 participants	2 participants	0 participants	5 participants	0 participants
Dose Limiting Toxicity (DLT) Grade 3 Anemia	0 participants	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: From the start of the treatment until disease progression/recurrence, assessed up to 24 months

Population: One patient from the escalation phase dose level 3, and two patients from the expansion phase dose level 2 were unevaluable for overall response.

ORR will be estimated along with 95% exact binomial confidence interval.

Outcome measures

Outcome measures
Measure	Escalation Phase n=3 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase n=11 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) n=2 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) n=12 Participants Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Overall Response Rate (ORR)	33.3 percentage of participants	18.2 percentage of participants	0 percentage of participants	21.4 percentage of participants	—

SECONDARY outcome

Timeframe: Time from registration to time of progressive disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 criteria or death from any cause, whichever occurs first, assessed up to 24 months

Will be estimated using the Kaplan-Meier curve and median estimates and confidence intervals will be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from date of enrollment to the date of death due to any cause, assessed up to 24 months

Will be estimated using the Kaplan-Meier curve and median estimates and confidence intervals will be calculated.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

Will be summarized using descriptive statistics and changes from baseline versus follow-up time points will be assessed using paired test methodologies.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

Will be processed using the data processing and data analysis pipelines from the Biostatistics and Bioinformatics shared resource of Markey Cancer Center to identify candidate mutated genes with adjustment for false discovery rate.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

PK parameters will be estimated from patients enrolled in the dose escalation portion of the phase 1 trial. PK parameters will be compared with historical controls, and exploratorily, we may correlate exposure to toxicity, and incorporate data into a population PK model.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

Will be summarized by calculating the proportion of patients in each Krenning score category and exploratory assessments for association with clinical response (ORR) will be performed using Fisher's exact test. Median, interquartile range will be calculated for quantitative image measurements from gallium 68 dotatate and exploratory comparison of levels with clinical response (ORR) will be performed using two sample t-test or nonparametric analogs. Correlative endpoint analyses will be based on patients who received the recommended phase 2 dose from the dose escalation portion and expansion cohort.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 months

Will be assessed by paired t-test or other methods. Deoxynucleoside plasma concentration as a predictor of clinical outcomes will explored by linear (progression free survival) and logistic regression (response).

Outcome measures

Outcome data not reported

Adverse Events

Escalation Phase Dose Level 1 (100mg Triapine)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Escalation Phase Dose Level 2 (150mg Triapine)

Serious events: 8 serious events

Other events: 11 other events

Deaths: 2 deaths

Escalation Phase Dose Level 3 (200mg Triapine)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Expansion Phase Dose Level 1 (100mg Triapine)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Expansion Phase Dose Level 2 (150mg Triapine)

Serious events: 11 serious events

Other events: 14 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Escalation Phase Dose Level 1 (100mg Triapine) n=3 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 2 (150mg Triapine) n=11 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) n=1 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) n=2 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) n=14 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 • Up to 2 years	18.2% 2/11 • Number of events 2 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	28.6% 4/14 • Number of events 5 • Up to 2 years
Cardiac disorders Cardiac arrest	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	100.0% 1/1 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Hepatobiliary disorders Hepatic hemorrhage	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Investigations Blood bilirubin increased	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Investigations Lymphocyte count decreased	66.7% 2/3 • Number of events 3 • Up to 2 years	54.5% 6/11 • Number of events 6 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 2 • Up to 2 years	57.1% 8/14 • Number of events 9 • Up to 2 years
Investigations Neutrophil count decreased	33.3% 1/3 • Number of events 1 • Up to 2 years	27.3% 3/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	50.0% 7/14 • Number of events 7 • Up to 2 years
Investigations Platelet count decreased	33.3% 1/3 • Number of events 1 • Up to 2 years	27.3% 3/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	28.6% 4/14 • Number of events 4 • Up to 2 years
Investigations White blood cell decreased	33.3% 1/3 • Number of events 1 • Up to 2 years	36.4% 4/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	50.0% 7/14 • Number of events 7 • Up to 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Stroke	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Syncope	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 2 • Up to 2 years
Gastrointestinal disorders Colonic perforation	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Nausea	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Vomiting	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Infections and infestations Enterocolitis infectious	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Infections and infestations Peritoneal infection	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Investigations Alanine aminotransferase increased	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Acidosis	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years

Other adverse events

Other adverse events
Measure	Escalation Phase Dose Level 1 (100mg Triapine) n=3 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 2 (150mg Triapine) n=11 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Escalation Phase Dose Level 3 (200mg Triapine) n=1 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 1 (100mg Triapine) n=2 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO	Expansion Phase Dose Level 2 (150mg Triapine) n=14 participants at risk Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study. Biospecimen Collection: Correlative studies Computed Tomography: Undergo CT Lutetium Lu 177 Dotatate: Given IV Magnetic Resonance Imaging: Undergo MRI Triapine: Given PO
Cardiac disorders Tricuspid valve disease	33.3% 1/3 • Number of events 3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Bloating	33.3% 1/3 • Number of events 2 • Up to 2 years	18.2% 2/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Constipation	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 9 • Up to 2 years
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Up to 2 years	27.3% 3/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	28.6% 4/14 • Number of events 15 • Up to 2 years
Gastrointestinal disorders Flatulence	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 2 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 2 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 5 • Up to 2 years	81.8% 9/11 • Number of events 30 • Up to 2 years	100.0% 1/1 • Number of events 1 • Up to 2 years	100.0% 2/2 • Number of events 8 • Up to 2 years	35.7% 5/14 • Number of events 11 • Up to 2 years
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • Up to 2 years	18.2% 2/11 • Number of events 2 • Up to 2 years	100.0% 1/1 • Number of events 1 • Up to 2 years	100.0% 2/2 • Number of events 3 • Up to 2 years	21.4% 3/14 • Number of events 5 • Up to 2 years
General disorders Chills	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 2 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	14.3% 2/14 • Number of events 2 • Up to 2 years
General disorders Edema limbs	33.3% 1/3 • Number of events 2 • Up to 2 years	36.4% 4/11 • Number of events 10 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 13 • Up to 2 years	14.3% 2/14 • Number of events 9 • Up to 2 years
General disorders Fatigue	33.3% 1/3 • Number of events 4 • Up to 2 years	54.5% 6/11 • Number of events 34 • Up to 2 years	100.0% 1/1 • Number of events 1 • Up to 2 years	100.0% 2/2 • Number of events 19 • Up to 2 years	50.0% 7/14 • Number of events 24 • Up to 2 years
General disorders Fever	0.00% 0/3 • Up to 2 years	27.3% 3/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 2 • Up to 2 years
General disorders Flu like symptoms	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
General disorders General disorders and administration site conditions - Other	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Infections and infestations Infections and infestations - Other	0.00% 0/3 • Up to 2 years	27.3% 3/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Infections and infestations Skin infection	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Infections and infestations Upper respiratory infection	66.7% 2/3 • Number of events 6 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Injury, poisoning and procedural complications Bruising	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 6 • Up to 2 years	0.00% 0/14 • Up to 2 years
Injury, poisoning and procedural complications Wound complication	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Investigations Alanine aminotransferase increased	66.7% 2/3 • Number of events 5 • Up to 2 years	27.3% 3/11 • Number of events 8 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 5 • Up to 2 years	14.3% 2/14 • Number of events 2 • Up to 2 years
Investigations Alkaline phosphatase increased	100.0% 3/3 • Number of events 14 • Up to 2 years	18.2% 2/11 • Number of events 8 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	28.6% 4/14 • Number of events 16 • Up to 2 years
Investigations Aspartate aminotransferase increased	66.7% 2/3 • Number of events 2 • Up to 2 years	27.3% 3/11 • Number of events 8 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	28.6% 4/14 • Number of events 8 • Up to 2 years
Investigations Blood bilirubin increased	33.3% 1/3 • Number of events 1 • Up to 2 years	36.4% 4/11 • Number of events 7 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	57.1% 8/14 • Number of events 14 • Up to 2 years
Investigations Blood lactate dehydrogenase increased	33.3% 1/3 • Number of events 2 • Up to 2 years	45.5% 5/11 • Number of events 13 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 6 • Up to 2 years	35.7% 5/14 • Number of events 13 • Up to 2 years
Investigations Creatinine Increased	66.7% 2/3 • Number of events 2 • Up to 2 years	36.4% 4/11 • Number of events 24 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	14.3% 2/14 • Number of events 4 • Up to 2 years
Investigations Investigations - Other	33.3% 1/3 • Number of events 3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Investigations Lipase increased	33.3% 1/3 • Number of events 4 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Investigations Lymphocyte count decreased	100.0% 3/3 • Number of events 20 • Up to 2 years	90.9% 10/11 • Number of events 47 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 13 • Up to 2 years	78.6% 11/14 • Number of events 50 • Up to 2 years
Investigations Neutrophil count decreased	66.7% 2/3 • Number of events 9 • Up to 2 years	45.5% 5/11 • Number of events 16 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	42.9% 6/14 • Number of events 12 • Up to 2 years
Investigations Platelet count decreased	100.0% 3/3 • Number of events 14 • Up to 2 years	54.5% 6/11 • Number of events 24 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 4 • Up to 2 years	57.1% 8/14 • Number of events 33 • Up to 2 years
Investigations Weight gain	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 7 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 6 • Up to 2 years
Investigations Weight loss	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Investigations White blood cell decreased	100.0% 3/3 • Number of events 20 • Up to 2 years	63.6% 7/11 • Number of events 28 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 11 • Up to 2 years	71.4% 10/14 • Number of events 18 • Up to 2 years
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 7 • Up to 2 years	36.4% 4/11 • Number of events 9 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Metabolism and nutrition disorders Hyperglycemia	100.0% 3/3 • Number of events 7 • Up to 2 years	18.2% 2/11 • Number of events 7 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 6 • Up to 2 years	21.4% 3/14 • Number of events 10 • Up to 2 years
Metabolism and nutrition disorders Hypernatremia	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Metabolism and nutrition disorders Hypoalbuminnemia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 5 • Up to 2 years	28.6% 4/14 • Number of events 7 • Up to 2 years
Metabolism and nutrition disorders Hypocalcemia	66.7% 2/3 • Number of events 11 • Up to 2 years	18.2% 2/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	28.6% 4/14 • Number of events 6 • Up to 2 years
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 2 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	21.4% 3/14 • Number of events 11 • Up to 2 years
Metabolism and nutrition disorders Hypokalemia	66.7% 2/3 • Number of events 4 • Up to 2 years	18.2% 2/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 3 • Up to 2 years	21.4% 3/14 • Number of events 6 • Up to 2 years
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • Up to 2 years	18.2% 2/11 • Number of events 6 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 2 • Up to 2 years
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 7 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	14.3% 2/14 • Number of events 2 • Up to 2 years
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 10 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 4 • Up to 2 years
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Headache	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 6 • Up to 2 years
Nervous system disorders Paresthesia	0.00% 0/3 • Up to 2 years	36.4% 4/11 • Number of events 5 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 7 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 5 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 4 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Nervous system disorders Syncope	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Psychiatric disorders Anxiety	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Renal and urinary disorders Urinary frequency	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 7 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Renal and urinary disorders Urinary urgency	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Renal and urinary disorders Urine discolaration	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 4 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 4 • Up to 2 years	0.00% 0/14 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 2 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 5 • Up to 2 years	0.00% 0/14 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	100.0% 1/1 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 6 • Up to 2 years
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 8 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 4 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 8 • Up to 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Up to 2 years	18.2% 2/11 • Number of events 3 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Vascular disorders Flushing	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Vascular disorders Hypertension	0.00% 0/3 • Up to 2 years	27.3% 3/11 • Number of events 12 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	21.4% 3/14 • Number of events 11 • Up to 2 years
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Vascular disorders Thromboembolic event	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Cardiac disorders Atrial flutter	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 9 • Up to 2 years
Cardiac disorders Palpitations	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 5 • Up to 2 years	0.00% 0/14 • Up to 2 years
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 8 • Up to 2 years	0.00% 0/14 • Up to 2 years
Eye disorders Blurred vision	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 6 • Up to 2 years
Eye disorders Eye disorders -other	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 3 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	28.6% 4/14 • Number of events 11 • Up to 2 years
Gastrointestinal disorders Ascites	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 6 • Up to 2 years	0.00% 0/14 • Up to 2 years
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Gastrointestinal disorders Rectal pain	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 4 • Up to 2 years
General disorders Infusion site extravasation	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
General disorders Non-cardiac chest pain	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 4 • Up to 2 years
General disorders Pain	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 9 • Up to 2 years	0.00% 0/14 • Up to 2 years
Infections and infestations Thrush	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	7.1% 1/14 • Number of events 4 • Up to 2 years
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	0.00% 0/14 • Up to 2 years
Investigations INR increased	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Investigations Serum amylase increased	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 23 • Up to 2 years	7.1% 1/14 • Number of events 9 • Up to 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 4 • Up to 2 years
Nervous system disorders Dizziness	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 4 • Up to 2 years	21.4% 3/14 • Number of events 7 • Up to 2 years
Nervous system disorders Dysesthesia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 5 • Up to 2 years
Nervous system disorders Dysgeusia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 6 • Up to 2 years
Psychiatric disorders Insomnia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 3 • Up to 2 years
Renal and urinary disorders Dysuria	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years	7.1% 1/14 • Number of events 2 • Up to 2 years
Renal and urinary disorders Renal calculi	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 4 • Up to 2 years	0.00% 0/14 • Up to 2 years
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 5 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	7.1% 1/14 • Number of events 10 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 4 • Up to 2 years	0.00% 0/14 • Up to 2 years
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - other	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 3 • Up to 2 years	0.00% 0/14 • Up to 2 years
Vascular disorders Vascular disorders - other	0.00% 0/3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	50.0% 1/2 • Number of events 8 • Up to 2 years	0.00% 0/14 • Up to 2 years
Cardiac disorders Pericardial effusion	33.3% 1/3 • Number of events 3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Up to 2 years	9.1% 1/11 • Number of events 1 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Blood and lymphatic system disorders Anemia	100.0% 3/3 • Number of events 17 • Up to 2 years	90.9% 10/11 • Number of events 51 • Up to 2 years	0.00% 0/1 • Up to 2 years	100.0% 2/2 • Number of events 20 • Up to 2 years	85.7% 12/14 • Number of events 47 • Up to 2 years
Blood and lymphatic system disorders Methemoglobinemia	0.00% 0/3 • Up to 2 years	27.3% 3/11 • Number of events 16 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Cardiac disorders Aortic Valve Disease	33.3% 1/3 • Number of events 3 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years
Cardiac disorders Atrial Fibrillation	33.3% 1/3 • Number of events 1 • Up to 2 years	0.00% 0/11 • Up to 2 years	0.00% 0/1 • Up to 2 years	0.00% 0/2 • Up to 2 years	0.00% 0/14 • Up to 2 years

Additional Information

Dr. Susanne Arnold

University of Kentucky

Phone: 859-323-8043

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60