Back to resultsTrial of eRapa in Prostate Cancer Patients
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
eRapa (encapsulated rapamycin)
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
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
Sites / Locations
- UT Health San Antonio
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1: 0.5 mg weekly
Cohort 2: 1 mg weekly
Cohort 3: 0.5 mg daily
Cohort 4: 1 mg daily
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
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.
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
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.
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
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.
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
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.
Secondary Outcome Measures
Secondary Pharmacokinetics: AUC
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.
Secondary Pharmacokinetics: Exposure Trough Levels
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.
Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6
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.
Secondary Pharmacodynamics: mTOR inhibition upon initial dose
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.
Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing
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.
Secondary Pharmacodynamics: mTOR inhibition during final week 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.
Secondary Immunologic Response: T cell phenotype individually
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.
Secondary Immunologic Response: T cell function individually
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.
Secondary Immunologic Response: T cell phenotype within each dosing cohort
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.
Secondary Immunologic Response: T cell function within each dosing cohort
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.
Secondary Immunologic Response: T cell phenotype overall study-wide
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.
Secondary Immunologic Response: T cell function overall study-wide
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.
Secondary Quality of Life Analysis
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.
Full Information
NCT ID
NCT03618355
First Posted
June 12, 2018
Last Updated
March 30, 2020
Sponsor
Rapamycin Holdings, Inc. dba Emtora Biosciences
Collaborators
Cancer Insight, LLC
1. Study Identification
Unique Protocol Identification Number
NCT03618355
Brief Title
Trial of eRapa in Prostate Cancer Patients
Official Title
Phase Ib Trial of Encapsulated Rapamycin (eRapa) in Prostate Cancer Patients Under Active Surveillance
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 28, 2018 (Actual)
Primary Completion Date
December 2, 2019 (Actual)
Study Completion Date
December 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rapamycin Holdings, Inc. dba Emtora Biosciences
Collaborators
Cancer Insight, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to determine the safety, pharmacokinetics/pharmacodynamics, and immunologic impact of encapsulated rapamycin in patients with low risk prostate cancer under active surveillance. There will be four groups of patients, each receiving a different dose of rapamycin.
Detailed Description
This is a phase Ib trial of encapsulated rapamycin to determine safety, pharmacokinetics/pharmacodynamics, and immunologic impact in patients with low risk prostate cancer under active surveillance. This new formulation, encapsulated rapamycin (sirolimus), provides a more predictable bioavailability of this drug than [the other formulation]. The encapsulated and targeted rapamycin (eRapa) can be delivered at a consistent and lower dosage, not only improving the toxicity profile but also capitalizing on the newly appreciated mechanism of partial and/or intermittent mTOR inhibition, making eRapa an ideal immuno-oncologic and chemopreventative agent. Low dose rapamycin has been shown to prevent cancer formation, progression, and/or recurrence in the majority of cancer histologies including the most prevalent: lung, breast, prostate, and colon cancers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
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. With a single site screening patients into the cohorts at a rate of 3 patients every 6 weeks (4 weeks dosing and 2 weeks safety assessment), a new cohort will start approximately every 6 weeks. Therefore, if each cohort of 3 patients are pre-screened and there are no dose limiting toxicities (DLT), the 4th and final dose cohort will be enrolled at approximately 18 weeks. Each patient will be on study for 6 months; therefore, 10-11 months will be the shortest time for trial completion. Given unforeseen delays, we anticipate the trial to take approximately one year to complete.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: 0.5 mg weekly
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: 1 mg weekly
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3: 0.5 mg daily
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 4: 1 mg daily
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
eRapa (encapsulated rapamycin)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Description
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.
Time Frame
After 4 weeks of treatment in each dosing cohort.
Title
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Description
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.
Time Frame
After completion of treatment, approximately 12 weeks, in each dosing cohort.
Title
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Description
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.
Time Frame
This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur at 1 year.
Title
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
Description
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.
Time Frame
This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.
Secondary Outcome Measure Information:
Title
Secondary Pharmacokinetics: AUC
Description
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.
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.
Title
Secondary Pharmacokinetics: Exposure Trough Levels
Description
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.
Time Frame
Cohorts 3 and 4 PK analysis will occur during the first week of treatment.
Title
Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6
Description
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.
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.
Title
Secondary Pharmacodynamics: mTOR inhibition upon initial dose
Description
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.
Time Frame
Cohorts 1 and 2 PD analysis will occur during the first week.
Title
Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing
Description
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.
Time Frame
Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
Title
Secondary Pharmacodynamics: mTOR inhibition during final week of treatment
Description
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.
Time Frame
Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
Title
Secondary Immunologic Response: T cell phenotype individually
Description
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.
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).
Title
Secondary Immunologic Response: T cell function individually
Description
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.
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).
Title
Secondary Immunologic Response: T cell phenotype within each dosing cohort
Description
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.
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).
Title
Secondary Immunologic Response: T cell function within each dosing cohort
Description
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.
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).
Title
Secondary Immunologic Response: T cell phenotype overall study-wide
Description
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.
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).
Title
Secondary Immunologic Response: T cell function overall study-wide
Description
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.
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).
Title
Secondary Quality of Life Analysis
Description
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.
Time Frame
Assessments performed baseline, after completion of therapy (approximately 12 weeks), and after 6 months.
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Patient must have pathologically (histologically) proven diagnosis of prostate cancer with a Gleason score ≤7 (3+4) and already undergoing active surveillance.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George E Peoples, MD, FACS
Organizational Affiliation
Cancer Insight
Official's Role
Study Director
Facility Information:
Facility Name
UT Health San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Trial of eRapa in Prostate Cancer Patients
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