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| Name | Class |
|---|---|
| National Comprehensive Cancer Network | NETWORK |
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This is a single arm study of 11 men with treatment refractory metastatic Castrate Resistant Prostate Cancer (CRPC) who will receive temsirolimus IV at a dose of 25 mg weekly until progression. Progression will not include Prostate Specific Antigen (PSA) progression; however, upon PSA progression, the addition of an anti-androgen will be permitted. The primary objective of the study is to evaluate change in circulating tumor cell (CTC) counts over time in men with metastatic treatment-refractory CRPC in response to temsirolimus therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Temsirolimus 25 mg | Experimental | Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Temsirolimus | Drug | dosage form: IV dosage, frequency and duration: 25mg weekly until clinical progression |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer. | Median percent change in CTC count from baseline to 8 weeks of treatment. Percent change was calculated by determining the percentage increase or decrease in CTC count from baseline. | Baseline to 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in CTC Count From Baseline to 12 Weeks of Treatment. | To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy | Baseline to 12 weeks |
| Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew Armstrong, MD, ScM | Duke Unversity Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States | ||
| Virginia Oncology Associates |
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| ID | Title | Description |
|---|---|---|
| FG000 | Temsirolimus 25 mg | Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Temsirolimus 25 mg | Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Change in Circulating Tumor Cell (CTC) Counts in Men With Metastatic Treatment-refractory Castration-resistant Prostate Cancer. | Median percent change in CTC count from baseline to 8 weeks of treatment. Percent change was calculated by determining the percentage increase or decrease in CTC count from baseline. | CTC count at both baseline and week 8 were assessable in 8 of the 11 patients as CTCs were collected at both time points in these patients. Missing CTC data for 3 of the 11 patients due to laboratory error or no CTC available at various time points. | Posted | Median | Inter-Quartile Range | percent change | Baseline to 8 weeks |
|
2 years
The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov
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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 | Temsirolimus 25 mg | Temsirolimus 25mg was administered by IV infusion each week (days 1, 8, 15, and 22 of each 28 day cycle). The infusion was to be administered over a period not less than 30 minutes and was to be completed within 60 minutes. Subjects were premedicated with 25 to 50 mg IV or PO diphenhydramine (or an alternative antihistamine in case of allergies) 30 minutes prior to the infusion. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Andrew Armstrong | Duke University Medical Center | 919-668-8108 | andrew.armstrong@dm.duke.edu |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D009362 | Neoplasm Metastasis |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D005832 | Genital Diseases, Male |
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| ID | Term |
|---|---|
| C401859 | temsirolimus |
| D004155 | Diphenhydramine |
| ID | Term |
|---|---|
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D001559 | Benzhydryl Compounds |
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| Diphenhydramine | Drug | Dosage form: IV or PO Dosage, frequency and duration: 25-50mg, 30 minutes prior to Temsirolimus infusion |
|
|
Measures of epithelial plasticity on CTCs in response to Mammalian Target of Rapamycin (mTOR) inhibition with temsirolimus, using genomic and protein immunohistochemical methodology. N-cadherin was measured in CTCs captured using the CellSearch profile kit. The proportion of CTCs expressing N-cadherin was calculated and divided by the total number of CD45-negative, pan cytokeratin (CK) - positive, and 4',6-diamidino-2-phenylindole (DAPI+) intact cells to give a fractional expression of N-cadherin. Results are reported as a percentage. |
| Baseline and 8 weeks |
| Percent Change in LDH | To evaluate and correlate changes in serum Lactate Dehydrogenase (LDH) with CTC count changes over time in men with Castrate Resistant Prostate Cancer (CRPC) treated with temsirolimus | Baseline to 12 weeks |
| Median Progression-Free Survival (PFS) | Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Clinical Trial Working Group 2 (PCWG2) criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Additionally, according to PCWG2 criteria, disease progression in bone is defined as 2 or more new lesions seen on bone scan compared with the baseline scan used for trial entry. Per PCWG2 guidelines, therapy was not discontinued solely due to a rise in PSA alone. | 2 years |
| Maximum Rate of Change of Prostate-Specific Antigen (PSA). | Percent change in PSA between baseline and the measurement time point where the largest change in PSA occurred. Note that a positive change (greater than 0) indicates an increase in PSA, and a negative change (less than 0) indicates a decrease. | Baseline to 7 months |
| Time to PSA Progression | Time in months from the start of study treatment to the date of first PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve. | 2 years |
| Time to Second PSA Progression After Addition of Anti-androgen Therapy | Time in months from the time of anti-androgen therapy to the date of second PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to second PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve. | 2 years |
| Change Over Time in CTC Gene Expression Profile | Percent change in CTC gene expression from baseline to 8 or 12 weeks of treatment. | 12 weeks |
| Safety and Tolerability of Temsirolimus | Total number of grade 3, 4, and 5 adverse events at least possibly related to temsirolimus therapy. Adverse events were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were converted to 4.0 for the purposes of reporting to ClinicalTrials.gov. | 2 years |
| Norfolk |
| Virginia |
| 23502 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Percent Change in CTC Count From Baseline to 12 Weeks of Treatment. | To evaluate the change in CTC counts upon the addition of an anti-androgen upon PSA progression while on temsirolimus therapy | Data were insufficient to evaluate this outcome. Outcome not available at 12 weeks. CTCs were not collected at week 12 and thus were not analyzed. | Posted | Baseline to 12 weeks |
|
|
| Secondary | Mean Percent of N-cadherin Expression at Baseline and 8 Weeks of Treatment. | Measures of epithelial plasticity on CTCs in response to Mammalian Target of Rapamycin (mTOR) inhibition with temsirolimus, using genomic and protein immunohistochemical methodology. N-cadherin was measured in CTCs captured using the CellSearch profile kit. The proportion of CTCs expressing N-cadherin was calculated and divided by the total number of CD45-negative, pan cytokeratin (CK) - positive, and 4',6-diamidino-2-phenylindole (DAPI+) intact cells to give a fractional expression of N-cadherin. Results are reported as a percentage. | N-cadherin expression at both baseline and 8 weeks was evaluable in 7 patients. | Posted | Median | Full Range | Percent expression | Baseline and 8 weeks |
|
|
|
| Secondary | Percent Change in LDH | To evaluate and correlate changes in serum Lactate Dehydrogenase (LDH) with CTC count changes over time in men with Castrate Resistant Prostate Cancer (CRPC) treated with temsirolimus | Data were insufficient to evaluate this outcome. Data not collected. This outcome was not performed due to availability and feasibility of the tests involved. | Posted | Baseline to 12 weeks |
|
|
| Secondary | Median Progression-Free Survival (PFS) | Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Clinical Trial Working Group 2 (PCWG2) criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Additionally, according to PCWG2 criteria, disease progression in bone is defined as 2 or more new lesions seen on bone scan compared with the baseline scan used for trial entry. Per PCWG2 guidelines, therapy was not discontinued solely due to a rise in PSA alone. | Posted | Median | 95% Confidence Interval | Months | 2 years |
|
|
|
| Secondary | Maximum Rate of Change of Prostate-Specific Antigen (PSA). | Percent change in PSA between baseline and the measurement time point where the largest change in PSA occurred. Note that a positive change (greater than 0) indicates an increase in PSA, and a negative change (less than 0) indicates a decrease. | Posted | Median | Full Range | Percent change | Baseline to 7 months |
|
|
|
| Secondary | Time to PSA Progression | Time in months from the start of study treatment to the date of first PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve. | Data were insufficient to evaluate this outcome. Data not collected. PSA responses were not observed in this study and PSA progression dates would essentially be the same as the radiographic PFS dates. | Posted | 2 years |
|
|
| Secondary | Time to Second PSA Progression After Addition of Anti-androgen Therapy | Time in months from the time of anti-androgen therapy to the date of second PSA progression . Patients alive who had not progressed as of the last follow-up or patients who had expired had time to second PSA progression censored at the last follow-up date or death date. The median was estimated using a Kaplan-Meier curve. | Data were insufficient to evaluate this outcome. Data not collected. Patients progressed radiographically before 2nd PSA progression occurred. | Posted | 2 years |
|
|
| Secondary | Change Over Time in CTC Gene Expression Profile | Percent change in CTC gene expression from baseline to 8 or 12 weeks of treatment. | Data were insufficient to evaluate this outcome. Data not collected. This outcome was not performed due to availability and feasibility of the tests involved. | Posted | 12 weeks |
|
|
| Secondary | Safety and Tolerability of Temsirolimus | Total number of grade 3, 4, and 5 adverse events at least possibly related to temsirolimus therapy. Adverse events were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were converted to 4.0 for the purposes of reporting to ClinicalTrials.gov. | Posted | Number | Adverse Events | 2 years |
|
|
|
| 4 |
| 11 |
| 9 |
| 11 |
| Lung infection- Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Stroke- Hemorrhagic | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vascular disorders - Subdural Hemorrhage | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Night blindness | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastrointestinal disorders - Lip Swelling | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Infection - Picc Line | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection- Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| INR increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Investigations - Fluid Overload | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Weight Loss | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoalbuminenima | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcinemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponaturemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain - Lower Extremities Bilateral | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain, Intermittant- Lower Left Quadrant | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Bilateral Jaw | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Bone | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Left Femur | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Left Hip / Low Back | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Left Hip / Thigh | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Left Shoulder | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Left Side | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Right Flank | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- Right jaw | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain- left flank area | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cognitive Disturbance | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders - Nightmares | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders- Restless Legs | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Renal and urinary disorders - Right hydonephrosis | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus disorder | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash - Groin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash - Right Arm and Leg | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash- Ankles | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash- Penis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Thromboembolic event- Pulmonary Embolism | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
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| D000091662 |
| Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| Title | Measurements |
|---|---|
|