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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00238 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 06-160 | |||
| MSKCC IRB 06-160 | |||
| MSKCC-06160 | |||
| CDR0000579559 | |||
| 06-160 | Other Identifier | Memorial Sloan-Kettering Cancer Center | |
| 7864 | Other Identifier | CTEP | |
| N01CM62205 | U.S. NIH Grant/Contract | View source | |
| N01CM62206 | U.S. NIH Grant/Contract | View source | |
| P30CA008748 | U.S. NIH Grant/Contract | View source |
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This phase II trial studies how well androgen deprivation therapy and vorinostat followed by radical prostatectomy works in treating patients with prostate cancer that has not spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin acetate, and leuprolide acetate, may lessen the amount of androgens made by the body. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving androgen deprivation therapy and vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVES:
I. To determine the rate of pathologic complete response in patients with localized prostate cancer treated with androgen depletion therapy (ADT) and oral vorinostat administered for a minimum of 6 weeks and maximum of 8 weeks before radical prostatectomy.
SECONDARY OBJECTIVES:
I. To determine and evaluate pre- and post-treatment levels of prostate-specific antigen (PSA), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-dulfate (DHEA-S) in blood.
II. To determine and evaluate pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate.
III. To determine and evaluate gene and protein expression analysis including androgen receptor (AR) target genes, PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and post-treatment radical prostatectomy.
IV. To determine and evaluate exploratory gene microarray analysis. V. To determine and evaluate the safety and tolerability of ADT in combination with vorinostat (SAHA) as assessed by physical examinations, adverse events, and laboratory assessments.
OUTLINE:
Patients receive bicalutamide orally (PO) once daily (QD) for 1 month and leuprolide acetate intramuscularly (IM) or goserelin acetate subcutaneously (SC) once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
After completion of study treatment, patients are followed every 3 months for up to 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (Antihormone therapy and enzyme inhibitor therapy) | Experimental | Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bicalutamide | Drug | Given PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic Complete Response at the Time of Surgery | The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer. | At 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Gleason Score | A Gleason score is the sum of two numbers. Pathologist determines where the cancer is most prominent and assigns the primary grade, the secondary grade is assigned based on where the cancer is next most prominent. A score from one to five is assigned for each area based on how aggressive the tumor appears. A tumor with cell that appear close to normal is assigned a low Gleason score (six or below). A tumor with cells that appear clearly different from those of a normal prostate is assigned a high Gleason score (seven or above). A system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the tumor is less likely to spread; a high Gleason score means the cancer tissue is very different from normal and the tumor is more likely to spread. |
| Measure | Description | Time Frame |
|---|---|---|
| Protein Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 | Up to 1 year | |
| Safety and Tolerability of Androgen Depletion Therapy in Combination With Vorinostat as Assessed by Physical Examinations, Adverse Events, and Laboratory Assessments. Please See Adverse Events Section. |
Inclusion Criteria:
Histologic documentation of prostatic adenocarcinoma in 3 or more biopsy cores, of which at least 1 core demonstrates > 30% involvement with tumor; confirmation of localized disease by magnetic resonance imaging (MRI) with endorectal probe if available
No evidence of distant disease on a:
Appropriate candidate for radical prostatectomy
White blood cell (WBC) > 3000/uL
Platelets > 150,000/uL
Creatinine < 2 mg/dL
Serum PSA < 100 ng/mL
Bilirubin < 1.5 X ULN (institutional upper limits of normal)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2 X ULN
Karnofsky performance status > 70%
Willingness to undergo pretreatment transrectal ultrasound-guided prostate needle biopsy (optional)
Willingness to use adequate contraceptive methods during study therapy and for at least 3 months after completion of therapy
Ability to understand and willingness to sign a written informed consent document
Exclusion Criteria:
Evidence of small-cell, transitional-cell, or neuroendocrine pathologic features
Prior hormonal therapy with (e.g. 5-alpha-reductase inhibitors, gonadotropin hormone releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens), chemotherapy, or herbal medications administered with the intent to treat the patient's malignancy
History of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would compromise compliance with study requirements
Currently active secondary malignancy (as determined by the treating physician) other than non-melanoma skin cancer
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| Name | Affiliation | Role |
|---|---|---|
| Susan Slovin | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA / Jonsson Comprehensive Cancer Center | Los Angeles | California | 90095 | United States | ||
| UCSF Medical Center-Parnassus |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) | Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Goserelin Acetate | Drug | Given SC |
|
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| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Leuprolide Acetate | Drug | Given IM |
|
|
| Therapeutic Conventional Surgery | Procedure | Undergo radical prostatectomy |
|
| Vorinostat | Drug | Given PO |
|
|
| Baseline |
| Levels of DHEA in Blood From Radical Prostatectomy Specimens | Up to 1 year |
| Levels of DHEA-S in Blood From Radical Prostatectomy Specimens | Up to 1 year |
| Levels of DHT in Blood From Radical Prostatectomy Specimens | Up to 1 year |
| Levels of PSA in Blood From Radical Prostatectomy Specimens | Up to 1 year |
| Levels of Testosterone in Blood From Radical Prostatectomy Specimens | Up to 1 year |
Adverse events will be monitored at each scheduled visit and throughout the study. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
| Up to 1 year |
| Gene Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 | Estimates and 95% confidence intervals for the proportion of patients with nondetectable levels of PSA and TMPRSS2 will be computed. | at 12 weeks |
| Gene Microarray Analysis | Up to 1 year |
| Levels of Testosterone in Prostate Tissue | Up to 1 year |
| Levels of DHT in Prostate Tissue | Up to 1 year |
| Levels of Androstenediol in Prostate Tissue | Up to 1 year |
| Levels of Androstenedione in Prostate Tissue | Up to 1 year |
| Levels of DHEA in Prostate Tissue | Up to 1 year |
| Levels of DHEA-S in Prostate Tissue | Up to 1 year |
| San Francisco |
| California |
| 94143 |
| United States |
| University of Chicago Comprehensive Cancer Center | Chicago | Illinois | 60637 | United States |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| UMDNJ - New Jersey Medical School | Newark | New Jersey | 07103 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| University of Wisconsin Hospital and Clinics | Madison | Wisconsin | 53792 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) | Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | Pathologic Complete Response at the Time of Surgery | The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer. | Posted | Count of Participants | Participants | At 12 weeks |
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| Secondary | Gleason Score | A Gleason score is the sum of two numbers. Pathologist determines where the cancer is most prominent and assigns the primary grade, the secondary grade is assigned based on where the cancer is next most prominent. A score from one to five is assigned for each area based on how aggressive the tumor appears. A tumor with cell that appear close to normal is assigned a low Gleason score (six or below). A tumor with cells that appear clearly different from those of a normal prostate is assigned a high Gleason score (seven or above). A system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the tumor is less likely to spread; a high Gleason score means the cancer tissue is very different from normal and the tumor is more likely to spread. | Posted | Median | 95% Confidence Interval | units on a scale | Baseline |
| ||||||||||||||||||||||||||||||||
| Secondary | Levels of DHEA in Blood From Radical Prostatectomy Specimens | Posted | Median | 95% Confidence Interval | ng/dL | Up to 1 year |
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| Secondary | Levels of DHEA-S in Blood From Radical Prostatectomy Specimens | Posted | Median | 95% Confidence Interval | mcg/dL | Up to 1 year |
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| Secondary | Levels of DHT in Blood From Radical Prostatectomy Specimens | Posted | Median | 95% Confidence Interval | ng/dL | Up to 1 year |
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| Secondary | Levels of PSA in Blood From Radical Prostatectomy Specimens | Posted | Median | 95% Confidence Interval | ng/mL | Up to 1 year |
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| Secondary | Levels of Testosterone in Blood From Radical Prostatectomy Specimens | Posted | Median | 95% Confidence Interval | ng/dL | Up to 1 year |
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| Other Pre-specified | Protein Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Safety and Tolerability of Androgen Depletion Therapy in Combination With Vorinostat as Assessed by Physical Examinations, Adverse Events, and Laboratory Assessments. Please See Adverse Events Section. | Adverse events will be monitored at each scheduled visit and throughout the study. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | Not Posted | Up to 1 year | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Gene Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 | Estimates and 95% confidence intervals for the proportion of patients with nondetectable levels of PSA and TMPRSS2 will be computed. | Not Posted | at 12 weeks | Participants | |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Gene Microarray Analysis | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of Testosterone in Prostate Tissue | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of DHT in Prostate Tissue | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of Androstenediol in Prostate Tissue | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of Androstenedione in Prostate Tissue | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of DHEA in Prostate Tissue | Not Posted | Up to 1 year | Participants | ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Levels of DHEA-S in Prostate Tissue | Not Posted | Up to 1 year | Participants |
Up to 30 days after treatment
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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 | Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) | Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO | 2 | 19 | 17 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombosis | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Cardiac disorders-Other, specify | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Confusion | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypokalemia | 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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| INR increased | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Neutrophil count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Susan Slovin | Memorial Sloan Kettering Cancer Center | 646-422-4470 | slovins@mskcc.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 |
|---|---|
| C053541 | bicalutamide |
| D017273 | Goserelin |
| D016729 | Leuprolide |
| C493311 | luprolide acetate gel depot |
| D000077337 | Vorinostat |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
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