Trial | NCT03618355  Report issue

Title

Trial of eRapa in Prostate Cancer Patients
Phase Ib Trial of Encapsulated Rapamycin (eRapa) in Prostate Cancer Patients Under Active Surveillance

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    15
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.
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.
Study Started
Aug 28
2018
Primary Completion
Dec 02
2019
Study Completion
Dec 02
2019
Last Update
Mar 31
2020

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and better bioavailability enables eRapa to consistently provide approximately 30% more drug than sirolimus (unpublished data).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.

Cohort 1: 0.5 mg weekly Experimental

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.

Cohort 2: 1 mg weekly Experimental

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.

Cohort 3: 0.5 mg daily Experimental

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.

Cohort 4: 1 mg daily Experimental

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.

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
No Results Posted