Trial Outcomes & Findings for Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer (NCT NCT02768701)

Last Updated: 2023-05-22

Results Overview

PFS is defined as the time from day1 of the study treatment until disease progression or death. Disease progression is defined as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images or assessment of the physician. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2023-05-22

Participant Flow

Subjects were enrolled at five institutions (UNC-Chapel Hill, University of Pittsburgh, Moses Cone, UNC-Rex Cancer Center, and George Washington University) from November, 2016 to February, 2018. All subjects started to receive study treatment in November 2016 although 2 subjects signed informed consent in October 2016.

A total of forty-nine subjects consented to the study, but eight were deemed to be ineligible and one subject has withdrawn the consent during screening. Forty subjects were enrolled and evaluable for toxicity and survival, and 39 subjects were evaluable for response.

Participant milestones

Participant milestones
Measure	Experimental: Single Arm Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
Overall Study STARTED	40
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Single Arm n=40 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants
ECOG performance status 0	24 Participants n=5 Participants
ECOG performance status 1	16 Participants n=5 Participants
Stage at diagnosis 0-III	30 Participants n=5 Participants
Stage at diagnosis IV	10 Participants n=5 Participants
Prior (neo)adjuvant therapy Yes	33 Participants n=5 Participants
Prior (neo)adjuvant therapy No	7 Participants n=5 Participants
Sites of metastatic disease Liver	12 Participants n=5 Participants
Sites of metastatic disease Lung	14 Participants n=5 Participants
Sites of metastatic disease Bone	18 Participants n=5 Participants
Sites of metastatic disease Lymph node	4 Participants n=5 Participants
Sites of metastatic disease Brain	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: The subjects received at least one dose of the study treatment were included.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=35 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
The Progression Free Survival (PFS)	1.8 months Interval 1.4 to 2.3	—	—

PRIMARY outcome

Timeframe: Up to 2 years

Population: The subjects received two doses of the study treatment.

Regulatory T cells (Tregs) are counted before the treatment start and during the treatment. Methods: Blood Sample collection.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=40 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 n=40 Participants Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 n=40 Participants Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment.	-3.3 Percent Change in Tregs Interval -67.1 to 258.3	10 Percent Change in Tregs Interval -62.0 to 143.5	21.7 Percent Change in Tregs Interval -54.0 to 169.9

SECONDARY outcome

Timeframe: Up to 2 years

Population: The subjects received at least one dose of the study treatment and treatments response was assessed.

ORR is defined as the percentage of patients with \[compete response (CR) + partial response (PR)\] per RECIST1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions;

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=39 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Overall Response Rate (ORR)	21 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: The subjects received at least one dose of the study treatment and treatments response was assessed.

DOR is defined as the time from documentation of tumor response by RECIST1.1 \[(CR) + (PR)\] to disease progression by RECIST 1.1. It will be measured from when the time measurement criteria are first met for complete response or partial response (whichever status is recorded first) until the first date of progressive disease or death. Patients who neither progress nor die will be censored on the date of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=39 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Duration of Response (DOR)	20.4 months Interval 2.0 to 34.0	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: The subjects received the study treatment, treatments response was assessed and/or followed up for more than 6 months.

DCR is defined as the percentage of participants, who achieve \[compete response (CR) + partial response (PR) and stable disease (SD) per RECIST1.1. If best response is SD, then it must last more than 6 months to be included in calculation of DCR, to be considered to have received clinical benefit from the treatment regimen. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=39 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Disease Control Rate (DCR)	28 Participants	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: All subjects who received at least one dose of treatment were included.

OS is defined as the time from D1 of study treatment to death from any cause.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=35 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Overall Survival (OS)	6.3 months Interval 2.8 to 9.3	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: Participants who received at least one cycle of study treatment were included.

Treatment Associated Toxicity is defined as the number of participants with Grade 3-4 adverse events associated with study treatment. Adverse Events were classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.

Outcome measures

Outcome measures
Measure	Experimental: Single Arm n=40 Participants Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.	C1D1-C2D1 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1	C1D2-C2D1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
Treatment Associated Toxicity White blood cell decreased	2 Participants	—	—
Treatment Associated Toxicity Pericardial tamponade	1 Participants	—	—
Treatment Associated Toxicity Pain	1 Participants	—	—
Treatment Associated Toxicity Neutrophil count decreased	2 Participants	—	—
Treatment Associated Toxicity Lymphocyte count decreased	1 Participants	—	—
Treatment Associated Toxicity Immune system disorders	1 Participants	—	—
Treatment Associated Toxicity Hypoalbuminemia	1 Participants	—	—
Treatment Associated Toxicity Headache	1 Participants	—	—
Treatment Associated Toxicity Generalized muscle weakness	1 Participants	—	—
Treatment Associated Toxicity Gastrointestinal disorders	1 Participants	—	—
Treatment Associated Toxicity Fatigue	3 Participants	—	—
Treatment Associated Toxicity Dyspnea	2 Participants	—	—
Treatment Associated Toxicity Dry mouth	1 Participants	—	—
Treatment Associated Toxicity Diarrhea	2 Participants	—	—
Treatment Associated Toxicity Colitis	1 Participants	—	—
Treatment Associated Toxicity Blood bilirubin increased	1 Participants	—	—
Treatment Associated Toxicity Aspartate aminotransferase increased	2 Participants	—	—
Treatment Associated Toxicity Anorexia	1 Participants	—	—
Treatment Associated Toxicity Anemia	2 Participants	—	—
Treatment Associated Toxicity Alkaline phosphatase increased	1 Participants	—	—
Treatment Associated Toxicity Alanine aminotransferase increased	1 Participants	—	—

Adverse Events

Experimental: Single Arm

Serious events: 18 serious events

Other events: 40 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: Single Arm n=40 participants at risk Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
Blood and lymphatic system disorders Anemia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Pericardial tamponade	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Myocardial infarction	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Supraventricular tachycardia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Vomiting	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Abdominal pain	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Colitis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Colonic perforation	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Pain	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Fever	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Infections and infestations - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Sepsis	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Investigations - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Alkaline phosphatase increased	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Lethargy	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Presyncope	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Seizure	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Nervous system disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Paresthesia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Renal and urinary disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.

Other adverse events

Other adverse events
Measure	Experimental: Single Arm n=40 participants at risk Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
Blood and lymphatic system disorders Anemia	70.0% 28/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Blood and lymphatic system disorders Leukocytosis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Blood and lymphatic system disorders Lymph node pain	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Cardiac disorders - Other, specify	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Palpitations	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Pericardial effusion	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Pericardial tamponade	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Sinus tachycardia	15.0% 6/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Cardiac disorders Supraventricular tachycardia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Ear and labyrinth disorders Hearing impaired	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Ear and labyrinth disorders Tinnitus	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Ear and labyrinth disorders Vertigo	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Endocrine disorders Endocrine disorders - Other, specify	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Endocrine disorders Hyperthyroidism	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Endocrine disorders Hypothyroidism	22.5% 9/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Eye disorders Blurred vision	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Eye disorders Dry eye	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Eye disorders Eye disorders - Other, specify	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Eye disorders Scleral disorder	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Abdominal distension	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Abdominal pain	20.0% 8/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Ascites	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Bloating	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Colitis	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Constipation	52.5% 21/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Diarrhea	30.0% 12/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Dry mouth	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Dyspepsia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Dysphagia	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Gastroesophageal reflux disease	22.5% 9/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Mucositis oral	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Nausea	50.0% 20/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Oral dysesthesia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Gastrointestinal disorders Vomiting	17.5% 7/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Chills	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Edema face	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Edema limbs	32.5% 13/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Fatigue	75.0% 30/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Fever	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Flu like symptoms	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders General disorders and administration site conditions - Other, specify	17.5% 7/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Irritability	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Non-cardiac chest pain	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
General disorders Pain	27.5% 11/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Immune system disorders Immune system disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Infections and infestations - Other, specify	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Lung infection	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Mucosal infection	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Rash pustular	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Sinusitis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Upper respiratory infection	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Infections and infestations Urinary tract infection	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Injury, poisoning and procedural complications Bruising	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Injury, poisoning and procedural complications Fracture	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Injury, poisoning and procedural complications Spinal fracture	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Injury, poisoning and procedural complications Activated partial thromboplastin time prolonged	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Alanine aminotransferase increased	30.0% 12/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Alkaline phosphatase increased	20.0% 8/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Aspartate aminotransferase increased	42.5% 17/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Blood bilirubin increased	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Cholesterol high	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Creatinine increased	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Investigations - Other, specify	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Lymphocyte count decreased	62.5% 25/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Neutrophil count decreased	17.5% 7/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Platelet count decreased	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Weight gain	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations Weight loss	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Investigations White blood cell decreased	27.5% 11/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Acidosis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Anorexia	32.5% 13/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Dehydration	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Glucose intolerance	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypercalcemia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hyperglycemia	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hyperkalemia	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypernatremia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypoalbuminemia	37.5% 15/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypocalcemia	17.5% 7/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypoglycemia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypokalemia	22.5% 9/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypomagnesemia	25.0% 10/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hyponatremia	37.5% 15/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Hypophosphatemia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Arthralgia	15.0% 6/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Arthritis	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Back pain	20.0% 8/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Chest wall pain	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Flank pain	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Myositis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Neck pain	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Osteoporosis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 8/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Akathisia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Amnesia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Brachial plexopathy	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Dizziness	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Dysarthria	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Dysgeusia	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Headache	22.5% 9/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Memory impairment	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Nervous system disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Neuralgia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Paresthesia	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Peripheral motor neuropathy	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Peripheral sensory neuropathy	42.5% 17/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Presyncope	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Seizure	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Sinus pain	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Somnolence	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Nervous system disorders Tremor	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Agitation	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Anxiety	42.5% 17/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Confusion	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Depression	22.5% 9/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Insomnia	42.5% 17/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Libido decreased	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Psychiatric disorders Restlessness	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Renal and urinary disorders - Other, specify	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Urinary frequency	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Urinary incontinence	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Urinary urgency	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Renal and urinary disorders Urine discoloration	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Reproductive system and breast disorders Breast pain	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Reproductive system and breast disorders Pelvic pain	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Reproductive system and breast disorders Vaginal dryness	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	15.0% 6/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Cough	37.5% 15/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Dyspnea	42.5% 17/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Hoarseness	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Pleural effusion	20.0% 8/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Sinus disorder	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Sleep apnea	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Sore throat	7.5% 3/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Voice alteration	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Respiratory, thoracic and mediastinal disorders Wheezing	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Alopecia	15.0% 6/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Body odor	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Dry skin	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Pain of skin	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Pruritus	10.0% 4/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Rash acneiform	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Rash maculo-papular	17.5% 7/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	25.0% 10/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Skin and subcutaneous tissue disorders Surgical and medical procedures - Other, specify	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Flushing	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Hematoma	2.5% 1/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Hot flashes	12.5% 5/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Hypertension	40.0% 16/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Lymphedema	27.5% 11/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
Vascular disorders Thromboembolic event	5.0% 2/40 • From day 1 of the study treatment up to 3 years Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.

Additional Information

Melahat G. Canter MD MS ACRP-CP, Clinical Trial Analyst

University of North Carolina Lineberger Comprehensive Cancer Center

Phone: (919) 962-0000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60