Trial Outcomes & Findings for UARK 2014-14: Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment (NCT NCT02499081)

NCT ID: NCT02499081

Last Updated: 2021-06-11

Results Overview

To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: Baseline, Treatment (28-day cycles for 6 cycles)
• Results posted on: 2021-06-11

Participant Flow

Participant milestones

Measure	Ixazomib Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles.
Overall Study STARTED	20
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

UARK 2014-14: Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment

Baseline characteristics by cohort

Measure	Ixazomib n=20 Participants Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Age, Continuous	70.91 years STANDARD_DEVIATION 10.27 • n=93 Participants
Sex/Gender, Customized Male	11 participants n=93 Participants
Sex/Gender, Customized Female	9 participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	14 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	20 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline, Treatment (28-day cycles for 6 cycles)

To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma.

Outcome measures

Measure	Ixazomib n=20 Participants Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma.	20.00 ng/ML Interval 17.5 to 25.5

Adverse Events

Ixazomib

Serious events: 8 serious events

Other events: 20 other events

Deaths: 15 deaths

Serious adverse events

Measure	Ixazomib n=20 participants at risk Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Blood and lymphatic system disorders Anemia	40.0% 8/20 • Number of events 32 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Febrile Neutropenia	10.0% 2/20 • Number of events 3 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Lymphocyte Count Decreased	40.0% 8/20 • Number of events 44 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Neutrophil count decreased	10.0% 2/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Platelet count decreased	30.0% 6/20 • Number of events 65 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Wbc decrease (leukopenia)	10.0% 2/20 • Number of events 16 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Pain	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypermagnesemia	10.0% 2/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypokalemia	10.0% 2/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hyponatremia	10.0% 2/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Headache	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Syncope	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Psychiatric disorders Anxiety	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Vascular disorders Hypertension	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.

Other adverse events

Measure	Ixazomib n=20 participants at risk Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles. Ixazomib
Blood and lymphatic system disorders Anemia	55.0% 11/20 • Number of events 158 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Lymphocyte count decreased	25.0% 5/20 • Number of events 64 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Neutrophil count decreased	20.0% 4/20 • Number of events 11 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Platelet count decreased	70.0% 14/20 • Number of events 115 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Blood and lymphatic system disorders Wbc decrease (leukopenia)	50.0% 10/20 • Number of events 45 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Ear and labyrinth disorders Tinnitus	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Eye disorders Blurred vision	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Eye disorders Dry eye	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Eye disorders Eye disorders - other	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Eye disorders Photophobia	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Eye disorders Watering eyes	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Constipation	10.0% 2/20 • Number of events 4 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Diarrhea	45.0% 9/20 • Number of events 12 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Dyspepsia	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Gastroesophageal reflux disease	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Nausea	45.0% 9/20 • Number of events 9 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Gastrointestinal disorders Vomiting	15.0% 3/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Chills	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Edema limbs	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Fatigue	75.0% 15/20 • Number of events 27 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Fever	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Gait disturbance	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Malaise	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
General disorders Pain	5.0% 1/20 • Number of events 4 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Hepatobiliary disorders Alanine aminotransferase increased	15.0% 3/20 • Number of events 7 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Hepatobiliary disorders Alkaline phosphatase increased	35.0% 7/20 • Number of events 17 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Hepatobiliary disorders Aspartate aminotransferase increased	20.0% 4/20 • Number of events 14 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Hepatobiliary disorders Blood bilirubin increased	10.0% 2/20 • Number of events 6 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Hepatobiliary disorders Hypoalbuminemia	80.0% 16/20 • Number of events 70 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Immune system disorders Infections and infestations - Other, specify	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Immune system disorders Upper respiratory infection	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Injury, poisoning and procedural complications Bruising	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Anorexia	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Bicarbonate decrease	35.0% 7/20 • Number of events 15 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypercalcemia	20.0% 4/20 • Number of events 8 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hyperglycemia	85.0% 17/20 • Number of events 92 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hyperkalemia	5.0% 1/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypocalcemia	60.0% 12/20 • Number of events 67 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypokalemia	30.0% 6/20 • Number of events 38 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypomagnesemia	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hyponatremia	40.0% 8/20 • Number of events 54 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Musculoskeletal and connective tissue disorders Back pain	25.0% 5/20 • Number of events 6 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 4/20 • Number of events 4 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Cognitive disturbance	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Dizziness	30.0% 6/20 • Number of events 6 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Headache	15.0% 3/20 • Number of events 4 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Neuralgia	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Peripheral sensory neuropathy	50.0% 10/20 • Number of events 10 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Transient ischemic attacks	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Nervous system disorders Tremor	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Psychiatric disorders Depression	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Psychiatric disorders Insomnia	20.0% 4/20 • Number of events 4 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Psychiatric disorders Psychiatric disorders - Other, specify	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Renal and urinary disorders Creatinine increased	60.0% 12/20 • Number of events 102 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Renal and urinary disorders Renal and urinary disorders - Other, specify	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Cough	15.0% 3/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 4/20 • Number of events 5 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Postnasal drip	25.0% 5/20 • Number of events 6 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Productive cough	15.0% 3/20 • Number of events 3 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Respiratory, thoracic and mediastinal disorders Sleep apnea	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Skin and subcutaneous tissue disorders Alopecia	5.0% 1/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Skin and subcutaneous tissue disorders Dry skin	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Skin and subcutaneous tissue disorders Pruritus	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Skin and subcutaneous tissue disorders Rash acneiform	10.0% 2/20 • Number of events 2 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Skin and subcutaneous tissue disorders Urticaria	5.0% 1/20 • Number of events 1 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.
Metabolism and nutrition disorders Hypermagnesemia	10.0% 2/20 • Number of events 7 • Pretreatment Events were collected from Baseline until initiation of study drug. Adverse Events (AEs) were collected from the start of the study drug through the end of study treatment (28-day cycles for 6 cycles or until disease progression/intolerable toxicity). A Pretreatment Event is any untoward medical occurrence in a patient or subject who has signed informed consent to participate in a study but before administration of any study medication. AEs are systematically collected and assessed throughout the study via monitoring clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical exam; or other appropriate tests/procedures. AEs may also be self-reported by the patient.

Additional Information

Maurizio Zangari, MD

University of Arkansas for Medical Sciences

Phone: 501-686-8274

Email: MZangari@uams.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place