COMbination of Bipolar Androgen Therapy and Nivolumab (COMBAT-CRPC)

• ClinicalTrials.gov Identifier: NCT03554317
• Recruitment Status: Completed
• First Posted: June 13, 2018
• Results First Posted: October 3, 2023
• Last Update Posted: February 20, 2024
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Castration-resistant Prostate Cancer; Metastatic Prostate Cancer; Prostate Cancer
• Interventions: Drug: Testosterone cypionate; Drug: Nivolumab
• Enrollment: 45

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg intramuscular (IM) every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Period Title: Overall Study
Started	45
Completed	37
Not Completed	8
Reason Not Completed
Withdrawal by Subject	1
PSA Progression	3
Radiographic Progression	4

Baseline Characteristics

Arm/Group Title		Bipolar Androgen Therapy + Nivolumab
Arm/Group Description		All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Baseline Participants		45
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	45 participants
		69; (51 to 86)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Female	0 0.0%
	Male	45 100.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 2.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 8.9%
	White	40 88.9%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	45 participants
		45 100.0%
Baseline PSA (ng/mL) [1]; Median (Full Range); Unit of measure: ng/mL
	Number Analyzed	45 participants
		57.6; (5.4 to 457)
		[1] Measure Description: Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in the blood. For this test, a blood sample is sent to a laboratory for analysis. The results are usually reported as nanograms of PSA per milliliter (ng/mL) of blood.
Gleason sum [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	≤ 7	11 24.4%
	8	8 17.8%
	9	18 40.0%
	10	5 11.1%
	Unknown	3 6.7%
		[1] Measure Description: For most prostate cancers, the Gleason sum ranges from 6 to 10. Gleason 6 is the least aggressive cancer type. Gleason 7 is intermediately aggressive. Gleason 8-10 is the most aggressive cancer type.
Visceral disease [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Yes	7 15.6%
	No	38 84.4%
		[1] Measure Description: Visceral disease is described as the presence of soft tissue lesions.
Lines of Prior Novel AR (androgen receptor) Targeted Therapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	1	21 46.7%
	≥2	24 53.3%
Prior Taxane Chemotherapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Yes	20 44.4%
	No	25 55.6%
≥2 Novel AR (Androgen Receptor) Targeted Therapy and Prior Taxane Chemotherapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Yes	15 33.3%
	No	30 66.7%

Outcome Measures

1. Primary Outcome

Title	Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy + Nivolumab
Description	Number of participants with PSA response to Bipolar Androgen Therapy + Nivolumab. PSA response is counted for participants with ≥ 50% decline in PSA from baseline.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Measure Type: Count of Participants; Unit of Measure: Participants
	18 40.0%

2. Secondary Outcome

Title	Safety of Bipolar Androgen Therapy + Nivolumab As Determined by the Number of CTCAEs ≥ Grade 3
Description	Number of participants that experience adverse events grade ≥ 3, as defined by Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Measure Type: Count of Participants; Unit of Measure: Participants
	5 11.1%

3. Secondary Outcome

Title	PSA Progression-Free Survival (PSA-PFS) to Bipolar Androgen Therapy + Nivolumab
Description	Number of months from the time of initiation on Bipolar Androgen Therapy + Nivolumab therapy until PSA increase of 25% over a nadir value, confirmed by a follow-up PSA at least 4 weeks apart.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: months
	4.0; (3.6 to 5.0)

4. Secondary Outcome

Title	Progression-Free Survival (PFS) to Bipolar Androgen Therapy + Nivolumab
Description	Median number of months from the time of the first dose to objective radiographic tumor progression or death, whichever comes first, as defined by RECIST 1.1 Criteria for progressive disease or death.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (5.4 to 6.8)

5. Secondary Outcome

Title	Objective Response Rate (ORR) to Bipolar Androgen Therapy + Nivolumab
Description	Percentage of patients achieving a complete or partial response in target lesions as defined by RECIST 1.1 Criteria.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Measure Type: Number; Unit of Measure: percentage of overall participants
	18

6. Secondary Outcome

Title	Durable Progression-Free Survival (Durable PFS) to Bipolar Androgen Therapy + Nivolumab
Description	Number of participants without clinical/radiographic progression for > 6 months from the start of treatment.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Measure Type: Count of Participants; Unit of Measure: Participants
	15 33.3%

7. Secondary Outcome

Title	Median Overall Survival (OS) to Bipolar Androgen Therapy + Nivolumab
Description	Median number of months from study enrollment to death from any cause up to 2 years after the last dose of study treatment received.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description:	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
Overall Number of Participants Analyzed	45
Median (95% Confidence Interval); Unit of Measure: months
	24.4; (17.6 to 31.1)

8. Other Pre-specified Outcome

Title	PSA Response to Bipolar Androgen Therapy + Nivolumab in Patients With Gene Mutations
Description	Number of patients with ≥ 50% decline in PSA from baseline in patients with a somatic or germline mutation in homologous repair (HR) and/or mismatch repair (MMR) genes.
Time Frame	2 years

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	PSA Response to Bipolar Androgen Therapy + Nivolumab in Patients Without Gene Mutations
Description	Number of patients with ≥ 50% decline in PSA from baseline in patients without a somatic or germline mutation in homologous repair (HR) and/or mismatch repair (MMR) genes.
Time Frame	2 years

Outcome Measure Data Not Reported

10. Other Pre-specified Outcome

Title	Clinical Response Association of Bipolar Androgen Therapy + Nivolumab to Mutation-associated Neoantigens (MANAs).
Description	Clinical Response Association of Bipolar Androgen Therapy + Nivolumab to mutation-associated neoantigens (MANAs) can be assessed by the number of patients treated with Bipolar Androgen Therapy + Nivolumab with the presence of MANAs.
Time Frame	3 years

Outcome Measure Data Not Reported

11. Other Pre-specified Outcome

Title	Clinical Response Association to Bipolar Androgen Therapy + Nivolumab as Assessed by the Generation of Tumor-associated Neoantigens (TAAs)
Description	Clinical Response Association to Bipolar Androgen Therapy + Nivolumab with generation of tumor-associated neoantigens (TAAs) can be assessed by the number of patients treated with Bipolar Androgen Therapy + Nivolumab that have TAAs.
Time Frame	3 years

Outcome Measure Data Not Reported

12. Other Pre-specified Outcome

Title	PSA Correlation With Immune Markers in Response to Bipolar Androgen Therapy + Nivolumab
Description	Immunohistochemistry (IHC) staining will be used to quantify the number of immune markers present in pre-treatment and on-treatment biopsies in responders whose PSA has declined ≥ 50% versus non-responders.
Time Frame	2 years.

Outcome Measure Data Not Reported

13. Other Pre-specified Outcome

Title	PSA Correlation With DNA Damage Markers in Response to Bipolar Androgen Therapy + Nivolumab
Description	Immunohistochemistry (IHC) staining will be used to quantify the number of DNA damage markers present in pre-treatment and on-treatment biopsies in responders whose PSA has declined ≥ 50% versus non-responders.
Time Frame	2 years.

Outcome Measure Data Not Reported

14. Other Pre-specified Outcome

Title	Correlation of Bipolar Androgen Therapy on the Production of Inflammatory Chemokines and Cytokines
Description	Milliplex human cytokine/chemokine Immunology Multiplex Assay (Millipore-Sigma) will be used to assay acute effects of Bipolar Androgen Therapy by detecting the amount of cytokines and chemokines produced during therapy.
Time Frame	2 years.

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Adverse events were assessed up to 2 years. All-Cause Mortality was assessed up to 3 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Bipolar Androgen Therapy + Nivolumab
Arm/Group Description	All participants must have a rising PSA and/or radiographic progression and prior treatment with at least one novel androgen receptor (AR) targeted therapy (i.e. abiraterone acetate, enzalutamide). Up to one taxane agent for metastatic castration-resistant prostate cancer is permitted. Patients will be treated with testosterone cypionate 400mg IM every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg IV every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks. Treatment [with a minimum drug exposure of 12 weeks] will be continued until PSA progression (PCGW3 criteria) or clinical/radiographic progression (whichever comes first), or until unmanageable toxicity requiring drug cessation.
All-Cause Mortality
	Bipolar Androgen Therapy + Nivolumab
	Affected / at Risk (%)
Total	13/45 (28.89%)
Serious Adverse Events
	Bipolar Androgen Therapy + Nivolumab
	Affected / at Risk (%)	# Events
Total	11/45 (24.44%)
Blood and lymphatic system disorders
Leukocytosis *	1/45 (2.22%)	2
Blood lactate dehydrogenase increased *	1/45 (2.22%)	1
Cardiac disorders
Chest pain - cardiac *	1/45 (2.22%)	1
Pericardial effusion *	1/45 (2.22%)	1
Pericarditis *	1/45 (2.22%)	1
Gastrointestinal disorders
Abdominal pain *	1/45 (2.22%)	1
Diarrhea *	1/45 (2.22%)	1
Nausea *	2/45 (4.44%)	2
Rectal fistula *	1/45 (2.22%)	1
Vomiting *	1/45 (2.22%)	1
General disorders
Fever *	2/45 (4.44%)	2
Pain in extremity *	1/45 (2.22%)	1
Investigations
Investigations - Other, abnormal ECG *	1/45 (2.22%)	1
Metabolism and nutrition disorders
Hyponatremia *	1/45 (2.22%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness *	1/45 (2.22%)	1
Renal and urinary disorders
Acute kidney injury *	1/45 (2.22%)	1
Renal and urinary disorders - Other, left-sided renal obstruction *	1/45 (2.22%)	1
Urinary tract infection *	2/45 (4.44%)	2
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome *	1/45 (2.22%)	1
Lung infection *	1/45 (2.22%)	1
Pleural effusion *	1/45 (2.22%)	2
Pneumonitis *	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular *	1/45 (2.22%)	1
Vascular disorders
Hypertension *	1/45 (2.22%)	1
Vascular disorders - Other, deep vein thrombosis *	1/45 (2.22%)	1
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Bipolar Androgen Therapy + Nivolumab
	Affected / at Risk (%)	# Events
Total	45/45 (100.00%)
Blood and lymphatic system disorders
Anemia *	1/45 (2.22%)	4
Cardiac disorders
Atrial fibrillation *	1/45 (2.22%)	1
Chest pain - cardiac *	1/45 (2.22%)	1
Sinus tachycardia *	1/45 (2.22%)	1
Myocardial infarction *	1/45 (2.22%)	1
Ear and labyrinth disorders
Tinnitus *	1/45 (2.22%)	1
Vertigo *	1/45 (2.22%)	1
Endocrine disorders
Hyperthyroidism *	1/45 (2.22%)	1
Hypothyroidism *	5/45 (11.11%)	5
Eye disorders
Blurry vision *	1/45 (2.22%)	1
Conjunctivitis *	1/45 (2.22%)	1
Eye disorders - other, double vision *	1/45 (2.22%)	1
Uveitis *	1/45 (2.22%)	2
Gastrointestinal disorders
Bloating *	1/45 (2.22%)	45
Abdominal pain *	6/45 (13.33%)	6
Colitis *	2/45 (4.44%)	3
Constipation *	10/45 (22.22%)	10
Diarrhea *	9/45 (20.00%)	11
Dry mouth *	1/45 (2.22%)	1
Dyspepsia *	1/45 (2.22%)	1
Gastritis *	1/45 (2.22%)	1
Gastroesophageal reflux disease *	1/45 (2.22%)	2
Ileus *	1/45 (2.22%)	1
Nausea *	18/45 (40.00%)	19
Rectal fistula *	1/45 (2.22%)	1
Rectal pain *	1/45 (2.22%)	1
Vomiting *	7/45 (15.56%)	9
General disorders
Edema limbs *	1/45 (2.22%)	1
Edema face *	2/45 (4.44%)	2
Edema limbs *	11/45 (24.44%)	15
Fatigue *	10/45 (22.22%)	13
Fever *	2/45 (4.44%)	3
Flu like symptoms *	1/45 (2.22%)	1
Localized edema *	2/45 (4.44%)	2
Non-cardiac chest pain *	2/45 (4.44%)	2
Pain *	6/45 (13.33%)	13
Pain in extremity *	14/45 (31.11%)	23
Facial pain *	1/45 (2.22%)	1
Injection site reaction *	1/45 (2.22%)	1
Infections and infestations
Sinusitis *	1/45 (2.22%)	1
Thrush *	1/45 (2.22%)	1
Tooth infection *	1/45 (2.22%)	1
Injury, poisoning and procedural complications
Fall *	2/45 (4.44%)	2
Investigations
Alanine aminotransferase increased *	4/45 (8.89%)	4
Alkaline phosphatase increased *	2/45 (4.44%)	2
Serum amylase increased *	1/45 (2.22%)	3
Aspartate aminotransferase increased *	5/45 (11.11%)	5
Blood bilirubin increased *	2/45 (4.44%)	2
CPK increased *	4/45 (8.89%)	5
Creatinine increased *	7/45 (15.56%)	8
Investigations - Other, elevated white blood cells *	1/45 (2.22%)	1
Lipase increased *	4/45 (8.89%)	8
Serum amylase increased *	3/45 (6.67%)	4
Platelet count decreased *	2/45 (4.44%)	2
Metabolism and nutrition disorders
Anorexia *	3/45 (6.67%)	3
Anorexia *	1/45 (2.22%)	1
Dehydration *	1/45 (2.22%)	1
Hyperglycemai *	1/45 (2.22%)	1
Hyperkalemia *	1/45 (2.22%)	1
Hypokalemia *	1/45 (2.22%)	1
Hyponatremia *	1/45 (2.22%)	2
Hypophosphatemia *	1/45 (2.22%)	2
Musculoskeletal and connective tissue disorders
Arthralgia *	4/45 (8.89%)	8
Back pain *	14/45 (31.11%)	24
Generalized muscle weakness *	1/45 (2.22%)	1
Musculoskeletal and connective tissue disorders - other, restless legs *	1/45 (2.22%)	1
Myalgia *	4/45 (8.89%)	5
Bone pain *	3/45 (6.67%)	4
Flank pain *	3/45 (6.67%)	3
Nervous system disorders
Dysgeusia *	2/45 (4.44%)	2
Headache *	3/45 (6.67%)	3
Spinal cord compression *	1/45 (2.22%)	1
Tremor *	1/45 (2.22%)	1
Paresthesia *	1/45 (2.22%)	1
Psychiatric disorders
Depression *	1/45 (2.22%)	1
Dizziness *	3/45 (6.67%)	3
Insomnia *	1/45 (2.22%)	1
Irritability *	5/45 (11.11%)	5
Renal and urinary disorders
Dyspnea *	6/45 (13.33%)	6
Hematuria *	4/45 (8.89%)	4
Renal and urinary disorders - Other, hydrocalycosis *	1/45 (2.22%)	1
Kidney infection *	1/45 (2.22%)	1
Renal and urinary disorders - Other, urinary dysfunction *	1/45 (2.22%)	1
Urinary frequency *	3/45 (6.67%)	3
Urinary incontinence *	3/45 (6.67%)	4
Urinary retention *	3/45 (6.67%)	3
Urinary tract infection *	1/45 (2.22%)	5
Urinary tract obstruction *	1/45 (2.22%)	1
Urinary urgency *	1/45 (2.22%)	1
Reproductive system and breast disorders
Genital edema *	2/45 (4.44%)	2
Testicular disorder *	1/45 (2.22%)	1
Breast pain *	3/45 (6.67%)	3
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, acute hypoxic respiratory failure *	1/45 (2.22%)	2
Allergic rhinitis *	1/45 (2.22%)	1
Cough *	6/45 (13.33%)	6
Epistaxis *	1/45 (2.22%)	1
Lung infection *	1/45 (2.22%)	2
Nasal congestion *	4/45 (8.89%)	5
Pneumontiis *	1/45 (2.22%)	1
Sleep apnea *	2/45 (4.44%)	2
Upper respiratory infection *	1/45 (2.22%)	1
Pleuritic pain *	1/45 (2.22%)	1
Pleural effusion *	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders
Hypertrichosis *	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders - Other, macular rash *	1/45 (2.22%)	1
Pruritus *	3/45 (6.67%)	3
Rash maculo-papular *	2/45 (4.44%)	3
Skin and subcutaneous tissue disorders - Other, macular rash *	3/45 (6.67%)	3
Skin and subcutaneous tissue disorders - Other, pruritic rash *	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders - Other, follicular rash *	1/45 (2.22%)	1
Skin infection *	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders - Other, desquamation *	1/45 (2.22%)	1
Hyperhidrosis *	1/45 (2.22%)	1
Vascular disorders
Vascular disorders - Other, deep vein thrombosis *	1/45 (2.22%)	1
Flushing *	2/45 (4.44%)	2
Hot flashes *	1/45 (2.22%)	1
Hypertension *	3/45 (6.67%)	4
Hypotension *	1/45 (2.22%)	1
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

PI may not publish results before Sponsor/Sponsor PI. If no multicenter publication within 12 months from study completion or termination at all sites, PI may publish results as long as Sponsor PI has copy of communication for review and comment at least 30 days before submission. Sponsor may request PI hold communication for additional 65 days to allow for filing of patent application or other methods to preserve proprietary and/or patent rights.

Results Point of Contact

• Name/Title: Dr. Mark Markowski
• Organization: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
• Phone: 410-614-0567
• EMail: mmarko12@jhmi.edu

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT03554317
• Other Study ID Numbers: J1812; IRB00164973 ( Other Identifier: JHM IRB )
• First Submitted: May 23, 2018
• First Posted: June 13, 2018
• Results First Submitted: September 6, 2023
• Results First Posted: October 3, 2023
• Last Update Posted: February 20, 2024