Clinical trial NCT04331717: Bariatric Arterial Embolization for Men Starting Hormones for Prostate Cancer
Official title: BASH-PC: Bariatric Arterial Embolization for Men Starting Hormones for Prostate Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Prostate Adenocarcinoma
Obesity, Morbid
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Maryland Cigarette Restitution Fund
First posted: 2020-04-02
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The standard of care for obese men starting Androgen deprivation therapy (ADT) is physician based dietary and exercise counseling. Interventions to lessen the harmful effects of ADT are needed yet have been limited. Exercise is one strategy that has been attempted however there is conflicting data as to whether or not exercise effectively improves body mass, results in sustained weight loss, improvements in metabolic risk profiles including glucose tolerance and lipid profiles in men starting ADT, or has any effect of progression of cancer. Dietary interventions have been attempted without clear improvement in weight, metabolic factors, quality of life or cancer progression. Bariatric arterial embolization (BAE), given it results in weight loss in obese men and women without cancer, may be able to stave off the harmful side effects of ADT by inducing weight loss. Therefore, the investigators hypothesize that Bariatric Arterial embolization (BAE), done prior to initiation of ADT, will mitigate the weight gain and metabolic side effects associated with ADT, by inducing weight loss of at least 5% in obese men with biochemical recurrent prostate cancer starting ADT.

The primary objective is to determine if BAE, done prior to ADT initiation in obese men (with obesity related comorbid condition) with biochemically recurrent prostate cancer, can induce 5% or greater weight loss at 6 months.


Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information (HIPAA authorization will be included in the informed consent)
* Males aged 18 years of age and above
* Histological proof of adenocarcinoma of the prostate
* Non-metastatic disease by computed tomography (CT), magnetic resonance imaging (MRI) or Nuclear medicine (NM) bone scan. Patients must have CT abdomen/pelvis with contrast prior to enrollment.
* Metastatic disease may be permitted if NOT starting on any concomitant therapy (ie chemotherapy, anti-androgens)
* Prior local therapy with prostatectomy or radiotherapy (including brachytherapy) or both
* BMI \>30 kg/m2 with a concurrent obesity related comorbidity

Obesity related comorbidity is defined as:

* hypertension (resting blood pressure \>130/80 millimeters of mercury (mmHg) or being on medication to treat high blood pressure50),
* coronary artery disease (defined as prior myocardial infarction, elevated coronary artery calcium score, positive stress test history),
* dyslipidemia (triglyceride level of \>150mg/dL or being on medicine to treat high triglycerides; HDL \< 40mg/dL or being on medicine to treat cholesterol)51,
* diabetes (fasting glucose \>126mg/dL, A1c \> 6.5% or on medication for diabetes)52,
* pre-diabetes (fasting plasma glucose 100-125mg/dL)52,
* elevated waist circumference (\>40 inches in men),
* obstructive sleep apnea,
* arthritis, or
* non-alcoholic steatohepatitis.
* Prior salvage or adjuvant radiation therapy is allowed but must have been completed at least 3 months prior to enrollment
* Non-castrate levels of testosterone (\>50 ng/dL required)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
* Vascular anatomy (including celiac, hepatic and gastric arteries) that in the opinion of the interventional radiologist is amenable to bariatric embolization as assessed on 3D CT angiography
* Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelet count ≥ 50 x 109/L Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \< 2.5 x institutional upper limit of normal Estimated Glomerular filtration rate (GFR) \>60ml/min

Exclusion Criteria:

* Prior hormonal therapy within 12 months of enrollment
* Planned concurrent cytotoxic chemotherapy or antiandrogens (ex. bicalutamide, abiraterone acetate, enzalutamide or any investigational agent).
* Contraindication to the use of leuprolide, such as a previous hypersensitivity reaction to an Luteinizing hormone-releasing hormone (LHRH) analogue or any of the excipients in the leuprolide injection
* Prior history of gastric, pancreatic, hepatic and/or splenic surgery
* Prior radiation therapy to the upper abdomen (pelvic radiation is not an exclusion)
* Prior embolization to the stomach, spleen or liver
* Cirrhosis or known portal venous hypertension
* Active peptic ulcer disease or significant risk factors for peptic ulcer disease including daily NSAID use or daily smoking
* Hiatal hernia \>5cm in size
* Active h.pylori infection (patients will be required to have negative h.pylori testing)
* Weight \>400 pounds or BMI \>45kg/m2
* Known aortic arch pathology such as aneurysm or dissection
* Major comorbidity that precludes procedure including significant cardiovascular disease or peripheral arterial disease including the following:

Myocardial infarction within 6 months before screening Unstable angina within 3 months before screening New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months before the randomization date demonstrates a left ventricular ejection fraction ≥ 45% History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mm Hg or diastolic blood pressure \> 105 mm Hg at screening Peripheral arterial stenting or bypass procedure within 6 months before screening Active claudication

* Diabetes with A1c \>7% or requiring medication other than metformin
* Known gastric motility dysfunction
* Preexisting chronic abdominal pain
* Positive stool occult study
* Inflammatory bowel disease
* Known history of allergy to iodinated contrast media
* American Society of Anesthesiology (ASA) physical status classification system Class 4 of 5 (very high risk surgical candidates: class 4 = incapacitating disease that is a constant threat to life) at the time of screening for enrollment
* Any condition in which the principle investigator feels participation in the trial would put the patient and undue risk

Primary outcomes:
measure: Number of participants who experience at least 5 percent weight loss
timeFrame: At 6 months
Secondary outcomes:
measure: Number of adverse events
timeFrame: Up to 6 months
measure: Change in Blood Pressure
timeFrame: Baseline, weeks 4, 8, 12, 16, 20, 24, 36 and 48
measure: Change in Respiratory Rate
timeFrame: Baseline, weeks 4, 8, 12, 16, 20, 24, 36 and 48
measure: Change in Oxygen saturation
timeFrame: Baseline, weeks 4, 8, 12, 16, 20, 24, 36 and 48
Other outcomes:
measure: Time to disease progression
timeFrame: Up to 51 weeks
measure: Change in C-Reactive Protein level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Erythrocyte Sedimentation Rate
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Interleukin 6 level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Interleukin 8 level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Tumor Necrosis Factor Alpha level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Interleukin 1 alpha level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Interleukin 1 beta level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Ghrelin level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in leptin level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in active Glucagon-like Peptide-1 level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Peptide YY level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Insulin-like growth factor 1 level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Adiponectin level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in microbiome
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in high density lipoprotein level
timeFrame: At 12 weeks, 24 weeks, 36 weeks and 48 weeks
measure: Change in triglycerides level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in fasting glucose level
timeFrame: At 12 weeks, 24 weeks, 36 weeks and 48 weeks
measure: Change in hemoglobin A1c level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in low density lipoprotein level
timeFrame: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Quality of life as assessed by Abbreviated version of the medical outcomes, short-form 36 (SF-12)
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Quality of life as assessed by Impact of Weight on Quality of Life Questionnaire (IWQOL)
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Quality of life as assessed by Expanded Prostate Cancer Index Composite-26 question assessment (EPIC-26)
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks
measure: Change in Fatigue as assessed by the Brief Fatigue Inventory (BFI)
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Catherine Marshall, M.D.
role: PRINCIPAL_INVESTIGATOR
References: