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| ID | Type | Description | Link |
|---|---|---|---|
| CINJ-081001 | Other Identifier | CINJ | |
| CDR0000684276 | Registry Identifier | PDQ (Physician Data Query) |
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Drug was no longer available
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This partially randomized phase II trial is studying how well giving bicalutamide together with RO4929097 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bicalutamide together with RO4929097 may be an effective treatment for prostate cancer
PRIMARY OBJECTIVES:
I. To determine the difference in the time to PSA progression in patients with adenocarcinoma of the prostate who have rising PSA after definitive local therapy treated with bicalutamide with vs without gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097).
SECONDARY OBJECTIVES:
I. To determine the proportion of patients from each arm who achieve complete response (by PSA) during the combination phase.
II. To determine the proportion of patients from each arm with PSA progression during the combination phase.
III. To determine the time to PSA nadir during the combination phase for patients in each arm.
IV. To determine the time to PSA progression during the combination phase for patients in each arm.
V. To determine the time to PSA progression during the observation phase. VI. To determine the proportion of patients with PSA progression during the observation phase.
VII. To assess the safety and tolerability of gamma-secretase inhibitor RO4929097 in combination with bicalutamide.
VIII. To evaluate expression for targets of gamma secretase inhibitor in a prostate tissue microarray.
IX. To collect serum for future evaluation of soluble markers of gamma-secretase inhibition and angiogenesis.
OUTLINE: This is a multicenter study.
INDUCTION PHASE: All patients receive induction therapy comprising oral bicalutamide once daily for at least 16 weeks. Patients whose PSA declines at least 50% continue to the randomization phase.
RANDOMIZATION PHASE: Patients are stratified according to prior therapy (radiotherapy vs surgery) and randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.
ARM II: Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097) once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression.
Patients with no disease progression continue to the combination phase. Patients with disease progression undergo imaging studies to verify the absence of metastatic disease before continuing to the combination phase.
COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.
Blood and tumor tissue samples may be collected periodically for correlative studies. After completion of study treatment, patients are followed up every 6 weeks for 12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Placebo Comparator | Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. |
|
| Arm II | Experimental | Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Other | Given orally |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Time to PSA Progression | Time to PSA progression will be compared in the two groups using a log-rank test for a maximum of 54 weeks. | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Who Achieve Complete Response (by PSA) During the Combination Phase | Up to 12 months | |
| Proportion of Patients With PSA Progression During the Combination Phase | Up to 12 months |
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Inclusion Criteria:
Histologically confirmed prostate cancer
PSA progression after local treatment:
No metastatic disease on baseline bone scan and CT scan of the abdomen/pelvis
ECOG performance status 0-2
Life expectancy ≥ 6 months
WBC ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL
Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min for patients with creatinine levels above normal
Bilirubin normal
AST and/or ALT ≤ 2.5 times ULN
Serum total testosterone level ≥ 150 ng/dL
No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
Fertile patients must use two effective forms of contraception (i.e., barrier contraception and one other method of contraception) for 1 week before, during, and for ≥ 12 months after completion of study treatment
Able to swallow tablets
No malabsorption syndrome or other condition that would interfere with intestinal absorption
No uncontrolled concurrent illness including, but not limited to, any of the following:
Baseline QTc ≤ 450 msec
No serologic positivity for acute hepatitis A, acute or chronic hepatitis B, or acute or chronic hepatitis C
No history of liver disease or other forms of hepatitis or cirrhosis
No HIV-positive patients on combination antiretroviral therapy
No serious concurrent systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or bicalutamide
Patients may not donate sperm or blood during or for ≥ 12 months after completion of study treatment
No concurrent medications or food that may interfere with the metabolism of RO4929097 including grapefruit and fresh-squeezed grapefruit juice
Recovered from adverse events to < CTCAE grade 2
At least 3 months since prior and no concurrent androgen-deprivation therapy (ADT)
More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
More than 4 weeks since prior and no concurrent estrogens, estrogen-like substances (i.e., PC-SPES, saw palmetto, or other herbal product that may contain phytoestrogens), or any other hormonal therapy (including flutamide, nilutamide, finasteride, ketoconazole, systemic corticosteroids, megestrol acetate, or cyproterone acetate)
No other concurrent investigational agents
No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
No other investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or surgery for cancer
No concurrent hormonal therapy with a leuteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix)
No concurrent growth factors (e.g., G-CSF), packed RBC transfusions, or platelet transfusions
No concurrent antiarrhythmics or other medications known to prolong QTc
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| Name | Affiliation | Role |
|---|---|---|
| Mark Stein | UMDNJ - Robert Wood Johnson University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | 08903 | United States |
During the induction phase, if subjects do not have a decline in PSA ≥ 50%, they are taken off study. Subjects who have a PSA decline ≥ 50% are randomized to Arm I or Arm II.
A total of 19 patients were enrolled from a comprehensive cancer center in central New Jersey from August 2010 through November 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I - Placebo | Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. placebo: Given orally gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| gamma-secretase/Notch signalling pathway inhibitor RO4929097 |
| Drug |
Given orally |
|
|
| bicalutamide | Drug | Given orally |
|
|
| Time to PSA Nadir During the Combination Phase | Up to 12 months |
| Time to PSA Progression During the Combination Phase | Up to 12 months |
| Time to PSA Progression During the Observation Phase | Up to 12 months |
| Proportion of Patients With PSA Progression During the Observation Phase | Up to 12 months |
| Safety and Tolerability Assessed Using NCI CTCAE Version 4.0 | Number of participants randomized to RO4929097 arm who experienced serious adverse events . | Up to 12 months |
| FG001 | Arm II - RO4929097 | Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I | Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. placebo: Given orally gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally |
| BG001 | Arm II | Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to PSA Progression | Time to PSA progression will be compared in the two groups using a log-rank test for a maximum of 54 weeks. | Data were not collected as the protocol was terminated early due to lack of study drug. Only three patients progressed during randomization phase. | Posted | Up to 12 months |
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| Secondary | Proportion of Patients Who Achieve Complete Response (by PSA) During the Combination Phase | Data were not collected as study was terminated early due to lack of study drug. Only three patients started combination phase and were then removed from study due to lack of study drug. | Posted | Up to 12 months |
| ||||||||||||||||||||||||
| Secondary | Proportion of Patients With PSA Progression During the Combination Phase | Data were not collected as study was terminated early due to lack of study drug. Only three patients started combination phase and were then removed from study due to lack of study drug. | Posted | Up to 12 months |
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| Secondary | Time to PSA Nadir During the Combination Phase | Data were not collected as study was terminated early due to lack of study drug. | Posted | Up to 12 months |
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| Secondary | Time to PSA Progression During the Combination Phase | Data were not collected as study was terminated early due to lack of study drug. | Posted | Up to 12 months |
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| Secondary | Time to PSA Progression During the Observation Phase | Data were not collected as study was terminated early due to lack of study drug. No subjects entered the observation phase. | Posted | Up to 12 months |
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| Secondary | Proportion of Patients With PSA Progression During the Observation Phase | Data were not collected as study was terminated early due to lack of study drug. No subjects entered the observation phase. | Posted | Up to 12 months |
| ||||||||||||||||||||||||
| Secondary | Safety and Tolerability Assessed Using NCI CTCAE Version 4.0 | Number of participants randomized to RO4929097 arm who experienced serious adverse events . | Posted | Number | participants | Up to 12 months |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm I - Placebo | Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. placebo: Given orally gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally | 0 | 5 | 5 | 5 | ||
| EG001 | Arm II - RO4929097 | Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18 courses in the absence of PSA progression. COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally bicalutamide: Given orally | 0 | 5 | 4 | 5 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyphosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| lightheadedness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| hot flashes | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| constipation with blood | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| chest pain | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Breast tenderness | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Arthritic pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Bilateral eye infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Contact dermatitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Decreased lymphocytes | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Elevated Alkaline phosphatase | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Elevated ALT | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Erythematous right shin lesion | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Erythematous rash | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Gynecomastia | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
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| Hearing impairment | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
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| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| hyperbilirubinemia | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Low phosphorous | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Joint pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Kidney stone | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| leukopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
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| lymphopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Muscle pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Nocturia | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Nose bleed | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Proctitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Pruritic macular rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Rhinorrhea | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Right fore arm pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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Early termination leading to small numbers of subjects analyzed.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Stein, MD | Rutgers Cancer Institute of New Jersey | (732) 235-8675 | steinmn@cinj.rutgers.edu; zelinsta@cinj.rutgers.edu; rizzoji@cinj.rutgers.edu |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C545185 | 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide |
| C053541 | bicalutamide |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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