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Ganetespib is a drug that may stop cancer cells from growing. This drug has been used in other research studies and laboratory experiments. It has also been studied in phase I trials, where the appropriate dosing has been determined. Ganetespib is considered an "HSP90 inhibitor". By blocking HSP90, ganetespib is thought to reduce the ability of cancer cells to become resistant to treatment.
Fulvestrant is a hormonal therapy that works by attaching to estrogen receptors. In doing so, it can block the effect of estrogen on cancer cells. In addition, fulvestrant causes a decrease in the number of estrogen receptors. Fulvestrant is a drug that is approved by the FDA for treatment of metastatic, hormone receptor positive breast cancer, based upon the results of phase III clinical trials.
In the laboratory, adding ganetespib to fulvestrant appears to improve its effectiveness. It is not known whether this is true in humans. In this research study, we are evaluating the effect of the addition of ganetespib to fulvestrant in participants with hormone receptor-positive, metastatic breast cancer.
Because no one knows which of the study options is best, you will be "randomized" into one of the study groups: Arm A: Fulvestrant or Arm B: Fulvestrant plus Ganetespib. You will have a one-third chance of being placed in Arm A and a two-thirds chance of being placed in Arm B.
If you are initially placed in Arm A but your disease progresses, you will have the option of receiving the combination of fulvestrant plus ganetespib as part of Arm C.
You will undergo the following procedures during the research study: study drug(s), blood tests, clinical exams and scans/imaging tests.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM A - Fulvestrant | Active Comparator | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression. |
|
| Arm B - Fulvestrant+Ganetespib | Active Comparator | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fulvestrant | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD are censored at the date of last disease assessment. Participants who receive non-protocol anti-cancer therapy before disease progression are censored at time of last disease assessment. | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles longer-term. Participants in this study cohort were followed for survival up to 4 years from treatment end. |
| Measure | Description | Time Frame |
|---|---|---|
| Grade 3-4 Toxicity Rate | All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms were counted to calculate the percentage of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment. | AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nancy U Lin, MD | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| DFCI at Faulkner Hospital | Boston | Massachusetts | 02130 | United States | ||
| Brigham and Women's Hospital |
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Participants were enrolled between June 2012 and June 2015
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| ID | Title | Description |
|---|---|---|
| FG000 | ARM A - Fulvestrant | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression. |
| FG001 | Arm B - Fulvestrant+Ganetespib | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized Phase |
|
| ||||||||||||||||||
| Crossover Phase |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ARM A - Fulvestrant | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression. |
| 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 |
| 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 | Progression-Free Survival (PFS) | PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD are censored at the date of last disease assessment. Participants who receive non-protocol anti-cancer therapy before disease progression are censored at time of last disease assessment. | Posted | Mean | 95% Confidence Interval | months | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles longer-term. Participants in this study cohort were followed for survival up to 4 years from treatment end. |
|
AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 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 A - Fulvestrant | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic pain | Hepatobiliary disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nancy Lin | Dana-Farber Cancer Institute | 617-632-2335 | Nancy_Lin@dfci.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 14, 2015 | Aug 14, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077267 | Fulvestrant |
| C533237 | STA 9090 |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 |
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Participants were randomized 2:1 B Fulvestrant+Ganetespib:A Fulvestrant
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| Ganetespib |
| Drug |
|
|
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
| Clinical Benefit Rate (CBR) | CBR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration. | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
| Overall Survival (OS) | OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive or censored at date last known alive. | Participants were followed long-term for survival every 3 months from the end of treatment until death, lost to follow-up or up to 4 years from treatment end. Median survival follow-up was 28 months for the study cohort. |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| New Hampshire Oncology and Hematology, P.A. | Concord | New Hampshire | 03301 | United States |
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| NOT COMPLETED |
|
| BG001 |
| Arm B - Fulvestrant+Ganetespib |
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Arm B - Fulvestrant+Ganetespib | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression. |
|
|
|
| Secondary | Grade 3-4 Toxicity Rate | All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms were counted to calculate the percentage of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment. | Posted | Number | percentage of participants | AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
|
|
|
| Secondary | Objective Response Rate (ORR) | ORR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. | The analysis dataset is comprised of all enrolled participants. | Posted | Number | 95% Confidence Interval | percentage of participants | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
|
|
|
|
| Secondary | Clinical Benefit Rate (CBR) | CBR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration. | The analysis dataset is comprised of all enrolled participants. | Posted | Number | 95% Confidence Interval | percentage of participants | Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months. |
|
|
|
| Secondary | Overall Survival (OS) | OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive or censored at date last known alive. | The analysis dataset is comprised of all enrolled participants. | Posted | Median | 95% Confidence Interval | months | Participants were followed long-term for survival every 3 months from the end of treatment until death, lost to follow-up or up to 4 years from treatment end. Median survival follow-up was 28 months for the study cohort. |
|
|
|
| 11 |
| 15 |
| 2 |
| 15 |
| 15 |
| 15 |
| EG001 | Arm B - Fulvestrant+Ganetespib | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression. | 15 | 35 | 11 | 35 | 35 | 35 |
| EG002 | Arm A - Crossover Fulvestrant+Ganetespib | Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression. | 6 | 7 | 0 | 7 | 7 | 7 |
| Obstruction Gastric | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Lipase Increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Left hand tremors |
|
| Hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus Tachycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hematoma | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment | Liver bleed |
|
| Rash maculopapular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Acute coronary syndrome | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Infections and infestations-other | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Port infection |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vasovagal reaction | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| insomnia | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| hot flashes | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| anxiety | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| gastrointestinal disorders-other | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| injection site reaction | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| non-cardiac chest pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| alkaline phosphatase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| dysgeusia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| hematoma | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| infections and infestations-other | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |