Prostate Adenocarcinoma, Prostate Cancer, Prostate Cancer Recurrent
Conditions
Keywords
Prostate, Rising PSA, CBD Oil, Epidiolex
Brief summary
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.
Detailed description
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.
Interventions
DRUGEpidiolex Oral Liquid Product
600 mg Oral solution
Sponsors
Zin W Myint
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of localized therapy (prostatectomy or radiotherapy) for prostate adenocarcinoma (either histologically or cytologically confirmed) * Biochemical (PSA) recurrence, defined as: \* PSA of \>= 0.2 ng/ml that has increased above nadir following radical prostatectomy OR \* PSA increase of 2.0 ng/ml above post-therapy nadir after radiotherapy NOTE: PSA measured at two consecutive time points (separated by 4 or more weeks) is required in order to demonstrate the requisite increase in PSA * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Absolute neutrophil count \>= 1,500/microliters (at baseline \[pre-study\]) * Platelets \>= 80,000/microliters (at baseline \[pre-study\]) * Total bilirubin =\< institutional upper limit of normal (at baseline \[pre-study\]) * Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase) =\< institutional upper limit of normal (at baseline \[pre-study\]) * Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 using the Cockcroft-Gault formula (at baseline \[pre-study\]) * Patients with a prior or concurrent malignancy (non-prostate) whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by the treating physician are eligible * Given that worsening of an underlying state of mental depression or suicidal ideation has been reported with Epidiolex, patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support. Patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of Epidiolex hazardous, should not be enrolled on this protocol * Concurrent use of over-the-counter CBD oil, Marinol or marijuana is not permitted. Patients with a history of current over-the-counter CBD oil, Marinol or marijuana use for any reason are eligible only if they do the following: \* Complete a one-week washout period prior to study initiation \* Refrain from non-study related CBD oil, Marinol or marijuana use while on-study * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* History of hypersensitivity to Epidiolex (cannabidiol) or sesame seeds (one of the inactive ingredients in Epidiolex) * Any radiological evidence of metastatic disease (determined by standard of care computed tomography \[CT\] scans of abdomen. pelvis, chest, whole body bone scan or Axium positron emission tomography scan). Questionable lesions on bone scan will be confirmed by standard of care methods such as plain X-rays or Axium positron emission tomography scan, if not previously performed * Receipt of prior cytotoxic chemotherapy for recurrent prostate cancer * Use of androgen deprivation therapy (for example, bicalutamide, flutamide, nilutamide, or leuprolide acetate) concurrently or within the previous 3 months. * Uncontrolled intercurrent illness such as active infections. Other illnesses will be evaluated and eligibility status determined at the discretion of the treating physician and the investigator * Psychiatric illness/social situations that would limit compliance with study requirements * Concomitant use of valproate or clobazam * Concurrent use of over-the-counter CBD oil, Marinol or marijuana * Epidiolex is a moderate inhibitor of CYP2C19 and a moderate/strong inhibitor of CYP3A4, therefore concurrent use of CYP2C19 substrates is not allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | up to 90 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Biochemical Response. | within 90 days | Biochemical response (25% change from baseline) will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment. |
| Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response. | within 90 days | 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. |
| Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | 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) | Biochemical response will be determined by measurement of total testosterone level approximately every 4 weeks during treatment. |
| Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Baseline | 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. |
| Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Baseline | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 4 |
| 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 | 17 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Dose Escalation and Dose Expansion: Epidiolex 800 mg | Dose Escalation: Epidiolex 600 mg |
|---|---|---|---|
| Age, Continuous | 69 years | 71 years | 68 years |
| Prior treatment Prostatectomy Alone | 4 Participants | 3 Participants | 1 Participants |
| Prior treatment Prostatectomy and salvage radiation | 12 Participants | 10 Participants | 2 Participants |
| Prior treatment Radiation Alone | 5 Participants | 4 Participants | 1 Participants |
| Prior treatment Untreated | 0 Participants | 0 Participants | 0 Participants |
| PSA (ng/ml) | 1.25 ng/ml | 1.25 ng/ml | 1.84 ng/ml |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 14 Participants | 3 Participants |
| Region of Enrollment United States | 21 participants | 17 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 17 Participants | 4 Participants |
| Testosterone, total (ng/dL) | 325 mg/dL | 360 mg/dL | 214.5 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 17 |
| other Total, other adverse events | 2 / 2 | 9 / 17 |
| serious Total, serious adverse events | 0 / 2 | 0 / 17 |
Outcome results
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.
Time frame: up to 90 days
Population: Among 21 patients, a total of 18 patients were included in the efficacy analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | 0 Participants |
| Dose Escalation: Epidiolex 800 mg | Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | 0 Participants |
| Dose Expansion: Epidiolex 800 mg | Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0 | 0 Participants |
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.
Time frame: within 90 days
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response. | 0 nanograms per milliliter per year | Standard Deviation 0 |
| Dose Escalation: Epidiolex 800 mg | Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response. | 0 nanograms per milliliter per year | Standard Deviation 0 |
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.
Time frame: 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)
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Baseline | 388.3 ng/dL | Standard Deviation 270.7 |
| Dose Escalation: Epidiolex 600 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 3 | 253.92 ng/dL | Standard Deviation 249.61 |
| Dose Escalation: Epidiolex 600 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 1 | 421.94 ng/dL | Standard Deviation 238.67 |
| Dose Escalation: Epidiolex 600 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | 1 month post treatment | 434.0 ng/dL | Standard Deviation 252.8 |
| Dose Escalation: Epidiolex 600 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 2 | 345.21 ng/dL | Standard Deviation 157.02 |
| Dose Escalation: Epidiolex 800 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | 1 month post treatment | 190.0 ng/dL | Standard Deviation 76.4 |
| Dose Escalation: Epidiolex 800 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 1 | 190 ng/dL | Standard Deviation 76.37 |
| Dose Escalation: Epidiolex 800 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 2 | 242 ng/dL | Standard Deviation 14.14 |
| Dose Escalation: Epidiolex 800 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Cycle 3 | 208 ng/dL | Standard Deviation 36.77 |
| Dose Escalation: Epidiolex 800 mg | Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response | Baseline | 214.5 ng/dL | Standard Deviation 30.4 |
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.
Time frame: Baseline
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Diarrhea | 7.8 units on a scale | Standard Deviation 14.6 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Financial Problems | 7.8 units on a scale | Standard Deviation 14.6 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Global Health Status/QOL | 78.4 units on a scale | Standard Deviation 15 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Physical Functioning | 92.9 units on a scale | Standard Deviation 11.9 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Role Functioning | 97.1 units on a scale | Standard Deviation 8.8 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Emotional Functioning | 94.1 units on a scale | Standard Deviation 9.2 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Cognitive Functioning | 93.1 units on a scale | Standard Deviation 10.3 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Social Funcitoning | 97.1 units on a scale | Standard Deviation 8.8 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Fatigue | 12.4 units on a scale | Standard Deviation 13 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Nausea/Vomiting | 1.0 units on a scale | Standard Deviation 4 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Pain | 15.7 units on a scale | Standard Deviation 21.6 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Dyspnea | 7.8 units on a scale | Standard Deviation 14.6 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Insomnia | 13.7 units on a scale | Standard Deviation 16.9 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Appetite Loss | 0.0 units on a scale | Standard Deviation 0 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Constipation | 3.9 units on a scale | Standard Deviation 11.1 |
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.
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Nausea/Vomiting | 1.4 units on a scale | Standard Deviation 4.8 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Pain | 13.9 units on a scale | Standard Deviation 17.2 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Global Health Status/QOL | 81.3 units on a scale | Standard Deviation 13.4 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Physical Functioning | 90.0 units on a scale | Standard Deviation 14.4 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Role Functioning | 93.1 units on a scale | Standard Deviation 13.2 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Emotional Functioning | 96.5 units on a scale | Standard Deviation 5.6 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Cognitive Functioning | 91.7 units on a scale | Standard Deviation 11.2 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Social Funcitoning | 95.8 units on a scale | Standard Deviation 10.4 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Fatigue | 16.7 units on a scale | Standard Deviation 18.7 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Dyspnea | 13.9 units on a scale | Standard Deviation 22.3 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Insomnia | 8.3 units on a scale | Standard Deviation 20.7 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Appetite Loss | 0.0 units on a scale | Standard Deviation 0 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Constipation | 13.9 units on a scale | Standard Deviation 17.2 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Diarrhea | 8.3 units on a scale | Standard Deviation 15.1 |
| Dose Escalation: Epidiolex 600 mg | Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30) | Financial Problems | 11.1 units on a scale | Standard Deviation 16.4 |
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.
Time frame: within 90 days
Population: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Participants With Biochemical Response. | stable biochemical disease | 2 Participants |
| Dose Escalation: Epidiolex 600 mg | Participants With Biochemical Response. | partial biochemical response | 0 Participants |
| Dose Escalation: Epidiolex 600 mg | Participants With Biochemical Response. | PSA progression | 0 Participants |
| Dose Escalation: Epidiolex 800 mg | Participants With Biochemical Response. | stable biochemical disease | 14 Participants |
| Dose Escalation: Epidiolex 800 mg | Participants With Biochemical Response. | partial biochemical response | 1 Participants |
| Dose Escalation: Epidiolex 800 mg | Participants With Biochemical Response. | PSA progression | 1 Participants |
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.
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Hormonal Treatment Related Symptoms | 9.0 units on a scale | Standard Deviation 10.2 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Sexual activity | 63.9 units on a scale | Standard Deviation 21.1 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Urinary Symptoms | 17.5 units on a scale | Standard Deviation 11.2 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Incontinence aid | 22.2 units on a scale | Standard Deviation 19.2 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Bowel Symptoms | 7.6 units on a scale | Standard Deviation 8.3 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Sexual Functioning | 77.8 units on a scale | Standard Deviation 0 |
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.
Time frame: Baseline
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Urinary Symptoms | 17.9 units on a scale | Standard Deviation 12.7 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Incontinence aid | 9.5 units on a scale | Standard Deviation 16.3 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Bowel Symptoms | 6.4 units on a scale | Standard Deviation 8.1 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Hormonal Treatment Related Symptoms | 5.9 units on a scale | Standard Deviation 6 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Sexual activity | 67.6 units on a scale | Standard Deviation 22.3 |
| Dose Escalation: Epidiolex 600 mg | Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25) | Sexual Functioning | 56.9 units on a scale | Standard Deviation 26.8 |