- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03618355
Trial of eRapa in Prostate Cancer Patients
Phase Ib Trial of Encapsulated Rapamycin (eRapa) in Prostate Cancer Patients Under Active Surveillance
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229
- UT Health San Antonio
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
-
The patient must:
- Have pathologically (histologically) proven diagnosis of prostate cancer with a Gleason score ≤7 (3+4) and already undergoing active surveillance
- Be able to give informed consent
- Be age 18 or older
Exclusion Criteria:
- Prostate cancer with a Gleason score >7
- Unable to give informed consent
- Age < 18
- Immunosuppressed state (e.g., HIV, use of chronic steroids)
- Active, uncontrolled infections
- On medications with strong inhibitors or inducers of CYP3A4 and or P-gp.
- On agents known to alter rapamycin metabolism significantly (Appendix H)
- Have another cancer requiring active treatment (except basal cell carcinoma or squamous cell carcinoma of the skin)
- Individuals with a reported history of liver disease (e.g., cirrhosis)
- Individuals who are not a good candidate for active surveillance in their treating physician's opinion
- Have a medical condition (e.g., anemia, anticoagulated) for which repeated phlebotomy may be problematic.
- Uncontrolled hypertension.
Individuals that have abnormal screening vital organ function prior to enrollment
Liver Function Test
- Bilirubin >2.0
- Alkaline phosphatase >5x upper limit of normal (ULN)
- ALT/AST >2x ULN
Complete Blood Count:
- WBC elevated above the normal standard per the testing laboratory
- Hgb/Hct below the normal standards of the testing lab
- Platelets below the normal standards of the testing lab
- Total Cholesterol >240 mg/dL
- Triglycerides > 200 mg/dL
- Serum creatinine >2 and BUN >30
- Urinary protein: proteinuria >1+ on urinalysis or >1 gm/24hr
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: 0.5 mg weekly
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy. eRapa (encapsulated rapamycin) is dosed at 0.5 mg every week. |
The eRapa (encapsulated rapamycin) drug product consists of sub-micron rapamycin particles incorporated into poly(methyl methacrylate) polymer (Eudragit® L 100 / S 100). This improved formulation and better bioavailability enables eRapa to consistently provide approximately 30% more drug than sirolimus (unpublished data). Improved and predictable delivery allows for consistent and sustained lower dosing, which will result in an improved toxicity profile since the latter is proven to be related to blood concentration levels. This is a phase Ib trial in low risk (Gleason score ≤7 (3+4)) prostate cancer patients under active surveillance to establish dosage safety and treatment levels. |
Experimental: Cohort 2: 1 mg weekly
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy. eRapa (encapsulated rapamycin) is dosed at 1 mg every week. |
The eRapa (encapsulated rapamycin) drug product consists of sub-micron rapamycin particles incorporated into poly(methyl methacrylate) polymer (Eudragit® L 100 / S 100). This improved formulation and better bioavailability enables eRapa to consistently provide approximately 30% more drug than sirolimus (unpublished data). Improved and predictable delivery allows for consistent and sustained lower dosing, which will result in an improved toxicity profile since the latter is proven to be related to blood concentration levels. This is a phase Ib trial in low risk (Gleason score ≤7 (3+4)) prostate cancer patients under active surveillance to establish dosage safety and treatment levels. |
Experimental: Cohort 3: 0.5 mg daily
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy. eRapa (encapsulated rapamycin) is dosed at 0.5 mg daily. |
The eRapa (encapsulated rapamycin) drug product consists of sub-micron rapamycin particles incorporated into poly(methyl methacrylate) polymer (Eudragit® L 100 / S 100). This improved formulation and better bioavailability enables eRapa to consistently provide approximately 30% more drug than sirolimus (unpublished data). Improved and predictable delivery allows for consistent and sustained lower dosing, which will result in an improved toxicity profile since the latter is proven to be related to blood concentration levels. This is a phase Ib trial in low risk (Gleason score ≤7 (3+4)) prostate cancer patients under active surveillance to establish dosage safety and treatment levels. |
Experimental: Cohort 4: 1 mg daily
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy. eRapa (encapsulated rapamycin) is dosed at 1 mg daily. |
The eRapa (encapsulated rapamycin) drug product consists of sub-micron rapamycin particles incorporated into poly(methyl methacrylate) polymer (Eudragit® L 100 / S 100). This improved formulation and better bioavailability enables eRapa to consistently provide approximately 30% more drug than sirolimus (unpublished data). Improved and predictable delivery allows for consistent and sustained lower dosing, which will result in an improved toxicity profile since the latter is proven to be related to blood concentration levels. This is a phase Ib trial in low risk (Gleason score ≤7 (3+4)) prostate cancer patients under active surveillance to establish dosage safety and treatment levels. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Time Frame: After 4 weeks of treatment in each dosing cohort.
|
To analyze the overall safety of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
|
After 4 weeks of treatment in each dosing cohort.
|
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Time Frame: After completion of treatment, approximately 12 weeks, in each dosing cohort.
|
To analyze the overall safety of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
|
After completion of treatment, approximately 12 weeks, in each dosing cohort.
|
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Time Frame: This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur at 1 year.
|
To compare safety between dosing cohorts of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 at the 4 week time point.
|
This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur at 1 year.
|
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Time Frame: This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.
|
To compare safety between dosing cohorts of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 at the 12 week time point.
|
This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary Pharmacokinetics: AUC
Time Frame: Cohorts 1 and 2 PK analysis will occur during the first week. Cohorts 3 and 4 PK analysis will occur during week 12 of treatment.
|
Pharmacokinetics of eRapa in blood will be evaluated throughout the trial and compared within and between the dosing cohorts.
For cohorts 1 and 2, single dose exposure curves will be generated by assessing the rapamycin levels in whole blood and spot card collection at 0, 0.5, 1, 2, 4, 6, 8, 24, 48, and 72 hrs after the first dose on week 1.
Cohorts 3 and 4, exposure curves will be generated during the last week of treatment with blood draws and spot card collection after a dose during the final week at 0, 0.5, 1, 1.5, and 2 hrs.
|
Cohorts 1 and 2 PK analysis will occur during the first week. Cohorts 3 and 4 PK analysis will occur during week 12 of treatment.
|
Secondary Pharmacokinetics: Exposure Trough Levels
Time Frame: Cohorts 3 and 4 PK analysis will occur during the first week of treatment.
|
Pharmacokinetics of eRapa in blood will be evaluated throughout the trial and compared within and between the dosing cohorts.
Cohorts 3 and 4, eRapa troughs will be gathered before the first 5 doses of eRapa during the week 1.
|
Cohorts 3 and 4 PK analysis will occur during the first week of treatment.
|
Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6
Time Frame: Cohorts 1 and 2 PD analysis will occur during the first week. Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Pharmacodynamics of eRapa in blood will be evaluated throughout the trial and compared within and between dosing cohorts.
For cohorts 1 and 2, mTOR inhibition in PBMC by assessment of phosphorylation of S6 will also be assessed at 0, 0.5, 1, 2, 4, 6, 8, 24, 48, and 72 hrs after the first dose on week 1.
Cohorts 3 and 4, mTor inhibitions will be gathered before the first 5 doses of eRapa during the week 1.
In addition, during the last week of treatment after a dose during the final week at 0, 0.5, 1, 1.5, and 2 hrs.
|
Cohorts 1 and 2 PD analysis will occur during the first week. Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Secondary Pharmacodynamics: mTOR inhibition upon initial dose
Time Frame: Cohorts 1 and 2 PD analysis will occur during the first week.
|
Pharmacodynamics of eRapa in blood will be evaluated throughout the trial and compared within and between dosing cohorts.
For cohorts 1 and 2, mTOR inhibition in PBMC by assessment of phosphorylation of S6 will also be assessed at 0, 0.5, 1, 2, 4, 6, 8, 24, 48, and 72 hrs after the first dose on week 1.
|
Cohorts 1 and 2 PD analysis will occur during the first week.
|
Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing
Time Frame: Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Pharmacodynamics of eRapa in blood will be evaluated throughout the trial and compared within and between dosing cohorts.
For cohorts 3 and 4, mTOR inhibition in PBMC by assessment of phosphorylation of S6 will also be assessed before the first 5 doses of eRapa during the week 1.
|
Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Secondary Pharmacodynamics: mTOR inhibition during final week of treatment
Time Frame: Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Pharmacodynamics of eRapa in blood will be evaluated throughout the trial and compared within and between dosing cohorts.
For cohorts 3 and 4, mTOR inhibition in PBMC by assessment of phosphorylation of S6 will also be assessed during the last week of treatment after a dose during the final week at 0, 0.5, 1, 1.5, and 2 hrs.
|
Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
|
Secondary Immunologic Response: T cell phenotype individually
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell naïve/memory/effector phenotype.
These results will be assessed individually.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Immunologic Response: T cell function individually
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell exhaustion markers (PD-1, LAG3, TIM3), and homing markers (CD62L, CCR7).
These results will be assessed individually.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Immunologic Response: T cell phenotype within each dosing cohort
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell naïve/memory/effector phenotype.
These results will be assessed within each dosing cohort.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Immunologic Response: T cell function within each dosing cohort
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell exhaustion markers (PD-1, LAG3, TIM3), and homing markers (CD62L, CCR7).
These results will be assessed within each dosing cohort.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Immunologic Response: T cell phenotype overall study-wide
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell naïve/memory/effector phenotype.
These results will be assessed overall study-wide.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Immunologic Response: T cell function overall study-wide
Time Frame: Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Immunologic response will be measured and compared from baseline at specified time points throughout the trial.
The specific analysis of T cell exhaustion markers (PD-1, LAG3, TIM3), and homing markers (CD62L, CCR7).
These results will be assessed overall study-wide.
|
Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).
|
Secondary Quality of Life Analysis
Time Frame: Assessments performed baseline, after completion of therapy (approximately 12 weeks), and after 6 months.
|
Quality of life will be assessed and compared to characterize the impact of eRapa before, during, and after treatment by using the National Institute of Health Patient-Reported Outcomes Measurement Information System (PROMIS-29) and Cognition (long form) assessments.
|
Assessments performed baseline, after completion of therapy (approximately 12 weeks), and after 6 months.
|
Collaborators and Investigators
Collaborators
Investigators
- Study Director: George E Peoples, MD, FACS, Cancer Insight
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Sirolimus
Other Study ID Numbers
- RHI-P01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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