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The purpose of this phase I/Ib study is to determine the safety profile of Epidiolex (CBD oil) in biochemically recurrent prostate cancer patients. The study consists of a dose escalation part and dose expansion part. The dose expansion part of the study will use the maximum tolerated dose (MTD) determined in the dose escalation part to assess the activity, safety and tolerability of the investigational product in patients with biochemically recurrent prostate cancer after localized therapy with either surgery or radiation.
Cannabinoids (CBD) have been widely used in medicines for centuries to control pain, nausea or vomiting, and to stimulate appetite, especially in cancer patients. Both cannabinoids receptor 1(CB1) and cannabinoids receptor 2 (CB2) were highly expressed in cultured prostate cancer cells compared to normal prostate cell lines. CBD inhibits tumor growth in xenograft model.
Clinicians have been challenged to improve the treatment of biochemically recurrent (BCR) prostate cancer in which prostatic specific antigen (PSA) rises without radiological or clinical progression years after localized treatment (radical prostatectomy or radiation therapy) with or without hormonal treatment. Approximately 50-90% of men with high-risk prostate cancer will experience a BCR. Based on the abovementioned preclinical observations of CBD's effect on prostate cancer and its safety data in two non-cancer populations, a phase I study of CBD in men with biochemically recurrent prostate cancer will be conducted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Experimental | Cohort 1 participants with rising PSA after failure of localized therapy will receive 600 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
|
| Dose Escalation: Epidiolex 800 mg | Experimental | Cohort 2 participants with rising PSA after failure of localized therapy will receive 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
|
| Dose Expansion: Epidiolex 800 mg | Experimental | Expansion Cohort participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epidiolex Oral Liquid Product | Drug | 600 mg Oral solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | DLT was defined as grade ≥3 nausea, vomiting, diarrhea that persists >72 h despite optimal anti-emetics and anti-diarrhea treatment, grade ≥3 hematological adverse events (AEs), or grade ≥2 suicidal ideation.Treatment-related adverse events are those that comprise a dose-limiting toxicity within 30 days after initiation of Epidiolex (i.e., acute DLT). Additionally, Treatment-related adverse events will continue to be monitored for a total of 90 days. | up to 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Participants With Biochemical Response. | Biochemical response (25% change from baseline) will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment. | within 90 days |
| Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response. |
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Inclusion Criteria:
Exclusion Criteria:
prostate cancer only occurs in male
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| Name | Affiliation | Role |
|---|---|---|
| Zin W. Myint, MD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Markey Cancer Center | Lexington | Kentucky | 40536 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: Dose Escalation: Epidiolex 600 mg | Cohort 1 participants with rising PSA after failure of localized therapy will receive 600 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
| FG001 | Experimental: Dose Escalation: Epidiolex 800 mg | Cohort 2 participants with rising PSA after failure of localized therapy will receive 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
| FG002 | Experimental: Dose Expansion: Epidiolex 800 mg | Expansion Cohort participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation: Epidiolex 600 mg | Cohort 1 participants with rising PSA after failure of localized therapy will receive 600 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
| 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 | Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | DLT was defined as grade ≥3 nausea, vomiting, diarrhea that persists >72 h despite optimal anti-emetics and anti-diarrhea treatment, grade ≥3 hematological adverse events (AEs), or grade ≥2 suicidal ideation.Treatment-related adverse events are those that comprise a dose-limiting toxicity within 30 days after initiation of Epidiolex (i.e., acute DLT). Additionally, Treatment-related adverse events will continue to be monitored for a total of 90 days. | Among 21 patients, a total of 18 patients were included in the efficacy analysis | Posted | Count of Participants | Participants | up to 90 days |
|
120 days
Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
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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 | Experimental: Dose Escalation: Epidiolex 600 mg | Cohort 1 participants with rising PSA after failure of localized therapy will receive 600 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Zin Myint | University of Kentucky | 8593233964 | zin.myint@uky.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 12, 2023 | May 2, 2023 | Prot_SAP_ICF_001.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Epidiolex Oral Liquid Product | Drug | 800 mg oral solution |
|
|
| Epidiolex Oral Liquid Product | Drug | 800 mg oral solution |
|
|
Biochemical response will be determined by measurement of PSA approximately every 4 weeks during treatment. PSA velocity is the calculation (PSA final measurement - PSA initial measurement) / number of years between measurements. |
| within 90 days |
| Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Biochemical response will be determined by measurement of total testosterone level approximately every 4 weeks during treatment. | Baseline, Day 1 of Cycle 1 (each cycle is 4 weeks), Day 1 of Cycle 2, Day 1 of Cycle 3, and 1 month post treatment (up to 16 weeks) |
| Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden. | Baseline |
| Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden. | 12 weeks |
| Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning. | Baseline |
| Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning. | 12 weeks |
| BG001 |
| Dose Escalation and Dose Expansion: Epidiolex 800 mg |
Cohort 2 participants with rising PSA after failure of localized therapy will receive 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex Expansion Cohort participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| PSA (ng/ml) | Median | Full Range | ng/ml |
|
| Testosterone, total (ng/dL) | Median | Full Range | mg/dL |
|
| Prior treatment | Count of Participants | Participants |
|
| OG001 | Dose Escalation: Epidiolex 800 mg | Cohort 2 participants with rising PSA after failure of localized therapy will receive 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex |
| OG002 | Dose Expansion: Epidiolex 800 mg | Expansion Cohort participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose |
|
|
| Secondary | Participants With Biochemical Response. | Biochemical response (25% change from baseline) will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment. | Patients who were DLT evaluable, had baseline measurements, and had at least one post-baseline measurement were included in the analysis of secondary endpoints. The assessments were combined for patients who received the recommended dose of 800 mg daily. | Posted | Count of Participants | Participants | within 90 days |
|
|
|
| Secondary | Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response. | Biochemical response will be determined by measurement of PSA approximately every 4 weeks during treatment. PSA velocity is the calculation (PSA final measurement - PSA initial measurement) / number of years between measurements. | Patients who were DLT evaluable, had baseline measurements, and had at least one post-baseline measurement were included in the analysis of secondary endpoints. The assessments were combined for patients who received the recommended dose of 800 mg daily. | Posted | Mean | Standard Deviation | nanograms per milliliter per year | within 90 days |
|
|
|
| Secondary | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Biochemical response will be determined by measurement of total testosterone level approximately every 4 weeks during treatment. | Patients who were DLT evaluable, had baseline measurements, and had at least one post-baseline measurement were included in the analysis of secondary endpoints. Data analysis for this outcome was combined in the 800 mg group | Posted | Mean | Standard Deviation | ng/dL | Baseline, Day 1 of Cycle 1 (each cycle is 4 weeks), Day 1 of Cycle 2, Day 1 of Cycle 3, and 1 month post treatment (up to 16 weeks) |
|
|
|
| Secondary | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden. | No data released for 600mg as only 1 participant answered QOL measures and confidentiality of health information could be impacted if the outcome measures were displayed. Only patients who received one or more doses of the recommended phase 2 dose (800 mg) and who completed one or more sections of the quality-of-life assessment were analyzed. Of the 17 patients who received the recommended dose of 800 mg daily, 17 completed patient-reported outcomes at baseline and 12 completed PROs at 12 weeks. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden. | No data released for 600mg as only 1 participant answered QOL measures and confidentiality of health information could be impacted if the outcome measures were displayed. Only patients who received one or more doses of the recommended phase 2 dose (800 mg) and who completed one or more sections of the quality-of-life assessment were analyzed. Of the 17 patients who received the recommended dose of 800 mg daily, 17 completed patient-reported outcomes at baseline and 12 completed PROs at 12 weeks. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
| Secondary | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning. | Assessments were combined and analyzed for patients who received one or more doses of the recommended phase 2 dose and who completed one or more sections of the quality-of-life assessment. For 800mg dose17 completed baseline and 12 completed at 12 weeks. Some participants left some questions blank (incontinence, sexual activity). No data released for 600mg as only 1 participant answered QOL measures, confidentiality of health information could be impacted if the outcome measures were displayed. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Secondary | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning. | Assessments were combined and analyzed for patients who received one or more doses of the recommended phase 2 dose and who completed one or more sections of the quality-of-life assessment. For 800mg dose17 completed baseline and 12 completed at 12 weeks. Some participants left some questions blank (incontinence, sexual activity). No data released for 600mg as only 1 participant answered QOL measures, confidentiality of health information could be impacted if the outcome measures were displayed. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
| 1 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Experimental: Dose Escalation and Expansion: Epidiolex 800 mg | Both Escalation and Expansion Cohorts participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose | 0 | 17 | 0 | 17 | 9 | 17 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | Systematic Assessment |
|
| Stomach Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Abnormal Liver Function Test | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Malaise | General disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Nervous system disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| PSA progression |
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| Cycle 1 |
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| Cycle 2 |
|
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| Cycle 3 |
|
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| 1 month post treatment |
|
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| Title | Measurements |
|---|---|
|
| Emotional Functioning |
|
| Cognitive Functioning |
|
| Social Funcitoning |
|
| Fatigue |
|
| Nausea/Vomiting |
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| Pain |
|
| Dyspnea |
|
| Insomnia |
|
| Appetite Loss |
|
| Constipation |
|
| Diarrhea |
|
| Financial Problems |
|
| Title | Measurements |
|---|---|
|
| Emotional Functioning |
|
| Cognitive Functioning |
|
| Social Funcitoning |
|
| Fatigue |
|
| Nausea/Vomiting |
|
| Pain |
|
| Dyspnea |
|
| Insomnia |
|
| Appetite Loss |
|
| Constipation |
|
| Diarrhea |
|
| Financial Problems |
|
| Incontinence aid |
|
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| Bowel Symptoms |
|
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| Hormonal Treatment Related Symptoms |
|
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| Sexual activity |
|
|
| Sexual Functioning |
|
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| Incontinence aid |
|
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| Bowel Symptoms |
|
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| Hormonal Treatment Related Symptoms |
|
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| Sexual activity |
|
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| Sexual Functioning |
|
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