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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA022453 | U.S. NIH Grant/Contract | View source | |
| WSU-2009-087 | |||
| NOVARTIS-WSU-2009-087 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving carboplatin together with everolimus and prednisone may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving carboplatin together with everolimus and prednisone works in treating patients with metastatic prostate cancer that progressed after docetaxel.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive carboplatin IV over 30-60 minutes on day 1, oral prednisone twice daily on days on days 1-21, and oral everolimus once daily on days 2-21 of course 1 and on days 1-21 of subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and tumor tissue samples are collected periodically for pharmacodynamic, pharmacokinetic, and biomarker analysis.
After completion of study treatment, patients are followed up every 3 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carboplatin, RAD 001 & Prednisone | Experimental | Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)*IV over 30-60 min, Day 1 of a 21 day cycle RAD 001: 5 mg Orally daily, starting from Day 2 continuously Prednisone 5 mg Orally twice daily, continuously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carboplatin | Drug | AUC = 5 by Calvert's formula, day 1 of each 21 day cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Progression (TTP) | Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria | Number of Participants with Grade 3/4 Toxicity as measured by NCI CTCAE v3.0 criteria | Day 1 of each cycle (every 21 days), through study completion, an average of 6 months |
| PSA Response Rate |
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DISEASE CHARACTERISTICS:
Histologically confirmed metastatic adenocarcinoma of the prostate
Objective disease progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal (when applicable)
Progressed after ≥ 1 prior docetaxel-based chemotherapy regimen for metastatic disease
Patients with measurable disease* must have either rising PSA, increase in size of the lesion(s), or both
Patients with no measurable disease must have a PSA ≥ 5 ng/mL or new areas of bony metastases on bone scan NOTE: *There is no minimum PSA requirement for patients with measurable disease
Documented to be castrate with a testosterone level of ≤ 0.5 ng/mL
No uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
PATIENT CHARACTERISTICS:
Zubrod performance status 0-1
ANC ≥ 1,500/mm^3
Hemoglobin ≥ 9.0 g/dL
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Calculated creatinine clearance ≥ 50 mL/min OR serum creatinine ≤ 2 mg/dL
AST and/or ALT ≤ 2.5 times ULN if alkaline phosphatase normal OR alkaline phosphatase ≤ 4 times ULN if AST and/or ALT normal (for patients without documented bone metastases or for patients with liver metastases)
AST and/or ALT < 2.5 times ULN, without regard to alkaline phosphatase levels (for patients with documented bone metastases)
Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 times ULN (in the case that one or both of these thresholds are exceeded, the patient is eligible only after initiation of appropriate lipid-lowering medication)
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
Willing and able to comply with this study
Able to ingest oral medication
No other malignancies except non-melanoma skin cancer or any other adequately treated cancer in complete remission for ≥ 2 years
No significant traumatic injury within the past 4 weeks
No active (acute or chronic) or uncontrolled severe infections
No severe and/or uncontrolled medical conditions or other conditions that could affect study participation, including the following:
No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to their excipients
No history of noncompliance to medical regimens
No uncontrolled diabetes mellitus
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
At least 1 prior docetaxel based regimen for metastatic disease
No more than 2 prior chemotherapy regimens for metastatic disease
No prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
At least 6 weeks since prior bicalutamide or nilutamide
At least 4 weeks since prior flutamide
More than 4 weeks since prior and no other concurrent investigational drugs
More than 4 weeks since prior and no other concurrent anticancer therapies (including chemotherapy, radiotherapy, or antibody-based therapy)
More than 4 weeks since prior and no concurrent major surgery (defined as requiring general anesthesia) and recovered
More than 1 week since prior and no concurrent immunization with attenuated live vaccines
No concurrent chronic, systemic treatment with corticosteroids or other immunosuppressive agents
No concurrent prophylactic growth factors
Concurrent bisphosphonate therapy allowed
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| Name | Affiliation | Role |
|---|---|---|
| Ulka N. Vaishampayan, M.D. | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northshore University Health System | Evanston | Illinois | 60201 | United States | ||
| Barbara Ann Karmanos Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26375845 | Derived | Vaishampayan U, Shevrin D, Stein M, Heilbrun L, Land S, Stark K, Li J, Dickow B, Heath E, Smith D, Fontana J. Phase II Trial of Carboplatin, Everolimus, and Prednisone in Metastatic Castration-resistant Prostate Cancer Pretreated With Docetaxel Chemotherapy: A Prostate Cancer Clinical Trial Consortium Study. Urology. 2015 Dec;86(6):1206-11. doi: 10.1016/j.urology.2015.08.008. Epub 2015 Sep 12. |
| Label | URL |
|---|---|
| Clinical trial summary from the National Cancer Institute's PDQ® database | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Carboplatin, RAD 001 & Prednisone | Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)*IV over 30-60 min, Day 1 of a 21 day cycle RAD 001: 5 mg Orally daily, starting from Day 2 continuously Prednisone 5 mg Orally twice daily, continuously carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle RAD 001: 5 mg orally starting on Day 2 then continuous prednisone: 5 mg orally twice a day starting on Day 1 then continuous laboratory biomarker analysis: Samples will be collected from archival tissue. pharmacological study: Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| RAD 001 | Drug | 5 mg orally starting on Day 2 then continuous |
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| prednisone | Drug | 5 mg orally twice a day starting on Day 1 then continuous |
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| laboratory biomarker analysis | Other | Samples will be collected from archival tissue. |
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| pharmacological study | Other | Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2 |
|
PSA response rate with response defined as => a 30% reduction in PSA |
| Day 1 of each cycle (every 21 days), through study completion, an average of 6 months |
| Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6) | PSA response defined as a decrease of 30% or more will be tabled against mTOR, pAKT, and p70S6 (1+, 2+, 3+ vs ND) | Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dose |
| Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample. | Using a limited sampling model (i.e., AUC = 0.52 × C2.75h + 0.92) (Sorensen et al., 1993), observed carboplatin AUC was estimated based on the concentration in the 2.75-h sample. | Samples were collected Cycle 2, Day 1 |
| Overall Survival | Overall Survival as measured by the Kaplan-Meier method | After treatment, participants will be contacted every 3 months up to 4 years |
| Detroit |
| Michigan |
| 48201-1379 |
| United States |
| Weisberg Cancer Treatment Center | Farmington Hills | Michigan | 48334 | United States |
| Cancer Institute of New Jersey | New Brunswick | New Jersey | 08903 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Carboplatin, RAD 001 & Prednisone | Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)*IV over 30-60 min, Day 1 of a 21 day cycle RAD 001: 5 mg Orally daily, starting from Day 2 continuously Prednisone 5 mg Orally twice daily, continuously carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle RAD 001: 5 mg orally starting on Day 2 then continuous prednisone: 5 mg orally twice a day starting on Day 1 then continuous laboratory biomarker analysis: Samples will be collected from archival tissue. pharmacological study: Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| 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 Progression (TTP) | Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Posted | Median | 90% Confidence Interval | months | Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease. |
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| Secondary | Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria | Number of Participants with Grade 3/4 Toxicity as measured by NCI CTCAE v3.0 criteria | Posted | Count of Participants | Participants | Day 1 of each cycle (every 21 days), through study completion, an average of 6 months |
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| ||||||||||||||||||||||||||||
| Secondary | PSA Response Rate | PSA response rate with response defined as => a 30% reduction in PSA | Posted | Number | 90% Confidence Interval | percentage of participants | Day 1 of each cycle (every 21 days), through study completion, an average of 6 months |
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| Secondary | Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6) | PSA response defined as a decrease of 30% or more will be tabled against mTOR, pAKT, and p70S6 (1+, 2+, 3+ vs ND) | There were only 2 responders of the 10 participants who were measured for mTOR, pAKT, and p70S6. | Posted | Number | participants | Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dose |
|
| |||||||||||||||||||||||||||
| Secondary | Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample. | Using a limited sampling model (i.e., AUC = 0.52 × C2.75h + 0.92) (Sorensen et al., 1993), observed carboplatin AUC was estimated based on the concentration in the 2.75-h sample. | Limited PK sampling for carboplatin were obtained at 2.75 and 24 h after the end of infusion from 8 patients. | Posted | Mean | Full Range | mg/ml*min | Samples were collected Cycle 2, Day 1 |
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| ||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall Survival as measured by the Kaplan-Meier method | Posted | Median | 90% Confidence Interval | months | After treatment, participants will be contacted every 3 months up to 4 years |
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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 | Carboplatin, RAD 001 & Prednisone | Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)*IV over 30-60 min, Day 1 of a 21 day cycle RAD 001: 5 mg Orally daily, starting from Day 2 continuously Prednisone 5 mg Orally twice daily, continuously carboplatin: AUC = 5 by Calvert's formula, day 1 of each 21 day cycle RAD 001: 5 mg orally starting on Day 2 then continuous prednisone: 5 mg orally twice a day starting on Day 1 then continuous laboratory biomarker analysis: Samples will be collected from archival tissue. pharmacological study: Samples will be collected Cycle 1, day 1, 2 & 8 and Cycle 2, Day 1 & 2 | 10 | 26 | 17 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Thrombosis_PE | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| AST | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypercholesterolemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Inf_wo_neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Edema | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Proteinuria | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| AST | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Sensory_Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypercholesterolemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Inf_wo_neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
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Small sample size; Correlates were conducted in <50% of the patients.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elisabeth I. Heath M.D. | Barbara Ann Karmanos Cancer Institute | 313-576-8717 | vaishamu@karmanos.org |
| 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 |
|---|---|
| D016190 | Carboplatin |
| D000068338 | Everolimus |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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