Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention 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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: eRapa (encapsulated rapamycin)
    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.
  • Drug: eRapa (encapsulated rapamycin)
    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.
  • Drug: eRapa (encapsulated rapamycin)
    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.
  • Drug: eRapa (encapsulated rapamycin)
    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.

Recruiting Locations

UT Health San Antonio
San Antonio, Texas 78229
Contact:
Brandi Weaver
210-567-0178
weaverb@uthscsa.edu

More Details

NCT ID
NCT03618355
Status
Recruiting
Sponsor
Rapamycin Holdings, Inc. dba Emtora Biosciences

Study Contact

Katie Lyon, MS, CCRP
210-952-6301
klyon@cancerinsight.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.