Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

• Sponsor: Mary-Ellen Taplin, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01393730
• Collaborator: (none)
• Enrollment: 40
• Locations: 4
• Arm: 1
• Duration (Months): 66.4
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if the addition of dutasteride to a regimen with abiraterone acetate and prednisone will improve on therapy in patients with castrate-resistant prostate cancer and metastatic disease. This study will also help determine the side effects of the study treatment and how often they occur.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Abiraterone acetate; Drug: Dutasteride; Drug: Prednisone	Phase 2

Detailed Description

Patients will receive abiraterone acetate and prednisone orally, once daily for 2 months (2 cycles) on an outpatient basis. At the start of cycle 3, dutasteride will be taken once daily. Patients will return to the clinic on Day 14 of the first 3 cycles for routine blood tests.

Patients will come to the clinic every 12 weeks for a CT scan and/or x-ray of the chest, CT scan or MRI of the abdomen and pelvis, bone scan, and blood test for testosterone and other specialized blood test.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Abiraterone Acetate Combined With Dutasteride With Correlative Assessment of Tumor Androgen Levels and Androgen Receptor Sequence and Signaling at Baseline and at Progression
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Mar 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abiraterone+prednisone+dutasteride Abiraterone acetate 1000mg orally once per day + prednisone 5mg orally once per day for two months, followed by abiraterone 1000mg orally once per day + prednisone 5mg orally once per day + dutasteride 3.5mg orally once per day in 28-day cycles until symptomatic or radiographic progression	Drug: Abiraterone acetate; Other Names: CB7630 ; Drug: Dutasteride; Other Names: Avodart ; Drug: Prednisone; Other Names: Corticosteroid

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Androgen Receptor (AR) Related Mutations [Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.]

   AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.

Secondary Outcome Measures

1. Change in Serum Levels of Testosterone [Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.]

   Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.

2. Prostate-Specific Antigen (PSA) Response [PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.]

   PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.

3. Time to PSA Progression [PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.]

   Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.

4. Best Overall Response [Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.]

   Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

5. Time to Progression (TTP) [Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint.]

   TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

6. Presence of AR Amplification [Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.]

   Presence of AR amplification was measured by established methods.

7. Change in Serum Androgen Levels [Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.]

   Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.

8. Change in Circulating Tumor Cells (CTCs) Levels [Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.]

   CTCs were measured based on established methods.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of adenocarcinoma of the prostate

• Castrate resistant disease

• Metastatic disease

• Normal organ and marrow function

• Subjects with partners of childbearing potential must be willing to use adequate methods of birth control

Exclusion Criteria:

• Uncontrolled intercurrent illness

• Uncontrolled hypertension

• Active or symptomatic viral hepatitis or chronic liver disease

• History of pituitary or adrenal dysfunction

• Clinically significant heart disease

• History of a different malignancy unless disease-free for at least 5 years

• Known brain metastasis

• History of gastrointestinal disorders

• Prior therapy with abiraterone acetate

• HIV-positive individuals on antiretroviral therapy

• Requirement for steroid use greater than the equivalent of 5 mg of prednisone daily

• Atrial fibrillation or other cardiac arrhythmia requiring therapy

• Thromboembolism in the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
4	University of Washington Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Mary-Ellen Taplin, MD

Investigators

• Principal Investigator: Mary-Ellen Taplin, M.D., Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01393730
• Other Study ID Numbers: 10-448
• First Posted: Jul 13, 2011
• Last Update Posted: Mar 15, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute: prostate; metastatic; castrate resistant
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Abiraterone Acetate; Dutasteride

Study Results

Participant Flow

Recruitment Details	Patients enrolled from September 2011 through October 2012

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Period Title: Overall Study
STARTED	40
Treated	38
Evaluable AR Amplification	21
Evaluable AR Mutation	14
COMPLETED	34
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Overall Participants	40
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	40 100%
Region of Enrollment (participants) [Number]
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Androgen Receptor (AR) Related Mutations
Description	AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.
Time Frame	Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all patients evaluable for AR mutation.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	14
Count of Participants [Participants]	1 2.5%

2. Secondary Outcome

Title	Change in Serum Levels of Testosterone
Description	Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.
Time Frame	Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Median (Inter-Quartile Range) [ng/dL]	0.25

3. Secondary Outcome

Title	Prostate-Specific Antigen (PSA) Response
Description	PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.
Time Frame	PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Count of Participants [Participants]	34 85%

4. Secondary Outcome

Title	Time to PSA Progression
Description	Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.
Time Frame	PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Median (95% Confidence Interval) [months]	5

5. Secondary Outcome

Title	Best Overall Response
Description	Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame	Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Count of Participants [Participants]	6 15%

6. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Median (95% Confidence Interval) [Months]	11

7. Secondary Outcome

Title	Presence of AR Amplification
Description	Presence of AR amplification was measured by established methods.
Time Frame	Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all evaluable patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	21
Count of Participants [Participants]	10 25%

8. Secondary Outcome

Title	Change in Serum Androgen Levels
Description	Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.
Time Frame	Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all treated patients.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	38
Median (Inter-Quartile Range) [ng/dl]	1.2

9. Secondary Outcome

Title	Change in Circulating Tumor Cells (CTCs) Levels
Description	CTCs were measured based on established methods.
Time Frame	Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Outcome Measure Data

Analysis Population Description

Data were not collected for this secondary endpoint.

Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Measure Participants	0

Adverse Events

Time Frame	Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Adverse Event Reporting Description	Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Arm/Group Title	Abiraterone + Prednisone + Dutasteride
Arm/Group Description	Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
All Cause Mortality
	Abiraterone + Prednisone + Dutasteride
	Affected / at Risk (%)	# Events
Total	0/38 (0%)
Serious Adverse Events
	Abiraterone + Prednisone + Dutasteride
	Affected / at Risk (%)	# Events
Total	12/38 (31.6%)
Cardiac disorders
Conduction abnormality/Atrioventricular heart block - AV block-second degree Mobitz Type II	1/38 (2.6%)
Cardiac disorders - Other, specify	1/38 (2.6%)
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Ureter	1/38 (2.6%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Vagina	1/38 (2.6%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	5/38 (13.2%)
Thromboembolic event	1/38 (2.6%)
Investigations
Alanine aminotransferase increased	1/38 (2.6%)
Lipase increased	1/38 (2.6%)
Lipase	1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Bone: spine-scoliosis	2/38 (5.3%)
Nervous system disorders
"Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Abiraterone + Prednisone + Dutasteride
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Bone marrow cellularity	2/38 (5.3%)
Lymphopenia	1/38 (2.6%)
Blood/Bone Marrow-Other (Specify)	1/38 (2.6%)
Cardiac disorders
Conduction abnormality/Atrioventricular heart block - Wolff-Parkinson-White syndrome	2/38 (5.3%)
Palpitations	1/38 (2.6%)
Cardiac disorders - Other, specify	1/38 (2.6%)
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders	1/38 (2.6%)
Ear and labyrinth disorders
External ear pain	1/38 (2.6%)
Tinnitus	1/38 (2.6%)
Ear and labyrinth disorders	1/38 (2.6%)
Eye disorders
Cataract	2/38 (5.3%)
Eye disorders - Other, specify	1/38 (2.6%)
Gastrointestinal disorders
Abdominal pain	2/38 (5.3%)
"Fistula, GI - Anus"	1/38 (2.6%)
"Fistula, GI - Esophagus"	7/38 (18.4%)
"Fistula, GI - Ileum"	4/38 (10.5%)
"Fistula, GI - Jejunum"	2/38 (5.3%)
"Fistula, GI - Stomach"	1/38 (2.6%)
Nausea	6/38 (15.8%)
"Obstruction, GI - Esophagus"	1/38 (2.6%)
"Stricture/stenosis (including anastomotic), GI - Duodenum"	5/38 (13.2%)
Gastrointestinal disorders - Other, specify	1/38 (2.6%)
General disorders
"Fatigue (asthenia, lethargy, malaise)"	1/38 (2.6%)
Obesity	1/38 (2.6%)
Sweating (diaphoresis)	22/38 (57.9%)
Weight gain	3/38 (7.9%)
Weight loss	3/38 (7.9%)
Localized edema	1/38 (2.6%)
Non-cardiac chest pain	1/38 (2.6%)
Pain	8/38 (21.1%)
General disorders and administration site conditions - Other, specify	1/38 (2.6%)
Infections and infestations
Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Brain	2/38 (5.3%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Liver	1/38 (2.6%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Nerve-peripheral	1/38 (2.6%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Peristomal	1/38 (2.6%)
Skin infection	2/38 (5.3%)
Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Upper aerodigestive NOS	1/38 (2.6%)
Urinary tract infection	2/38 (5.3%)
Injury, poisoning and procedural complications
Bruising	2/38 (5.3%)
Injury, poisoning and procedural complications	2/38 (5.3%)
Fracture	1/38 (2.6%)
Injury, poisoning and procedural complications - Other, specify	1/38 (2.6%)
Investigations
Alanine aminotransferase increased	7/38 (18.4%)
Alkaline phosphatase increased	1/38 (2.6%)
Aspartate aminotransferase increased	8/38 (21.1%)
Blood bilirubin increased	4/38 (10.5%)
Metabolism and nutrition disorders
Anorexia	3/38 (7.9%)
"Bicarbonate, serum-low"	6/38 (15.8%)
Hypocalcemia	1/38 (2.6%)
"Glucose, serum-high (hyperglycemia)"	12/38 (31.6%)
Musculoskeletal and connective tissue disorders
Bone: spine-scoliosis	3/38 (7.9%)
Extremity-lower (gait/walking)	7/38 (18.4%)
Extremity-upper (function)	5/38 (13.2%)
Fibrosis-cosmesis	1/38 (2.6%)
Fracture	1/38 (2.6%)
Local complication - device/prosthesis-related	2/38 (5.3%)
"Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-upper"	2/38 (5.3%)
Osteoporosis	4/38 (10.5%)
Soft tissue necrosis - Abdomen	1/38 (2.6%)
Soft tissue necrosis - Head	1/38 (2.6%)
Soft tissue necrosis - Neck	4/38 (10.5%)
Musculoskeletal/Soft Tissue-Other (Specify)	2/38 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/38 (2.6%)
Nervous system disorders
Irritability (children <3 years of age)	1/38 (2.6%)
"Leak, cerebrospinal fluid (CSF)"	2/38 (5.3%)
"Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"	2/38 (5.3%)
Nervous system disorders	1/38 (2.6%)
Nervous system disorders - Other, specify	2/38 (5.3%)
Psychiatric disorders
Insomnia	4/38 (10.5%)
Psychiatric disorders	1/38 (2.6%)
Renal and urinary disorders
"Leak (including anastomotic), GU - Kidney"	4/38 (10.5%)
"Leak (including anastomotic), GU - Spermatic cord"	2/38 (5.3%)
"Leak (including anastomotic), GU - Ureter"	1/38 (2.6%)
Renal and urinary disorders - Other, specify	1/38 (2.6%)
Reproductive system and breast disorders
Gynecomastia	2/38 (5.3%)
Testicular pain	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/38 (2.6%)
Cough	3/38 (7.9%)
Dyspnea	3/38 (7.9%)
Laryngeal fistula	1/38 (2.6%)
Prolonged intubation after pulmonary resection (>24 hrs after surgery)	3/38 (7.9%)
Pneumothorax	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders - Other, specify	2/38 (5.3%)
Skin and subcutaneous tissue disorders
Burn	1/38 (2.6%)
Hyperpigmentation	1/38 (2.6%)
Nail changes	1/38 (2.6%)
Rash: dermatitis associated with radiation - Chemoradiation	1/38 (2.6%)
Skin breakdown/decubitus ulcer	3/38 (7.9%)
Striae	2/38 (5.3%)
Ulceration	1/38 (2.6%)
Dermatology/Skin-Other (Specify)	4/38 (10.5%)
Surgical and medical procedures
Intra-operative injury - Pharynx	1/38 (2.6%)
Vascular disorders
Phlebitis (including superficial thrombosis)	2/38 (5.3%)
Portal vein flow	10/38 (26.3%)
Thrombosis/embolism (vascular access-related)	15/38 (39.5%)
Thrombosis/thrombus/embolism	2/38 (5.3%)

Limitations/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.