Trial of eRapa in Prostate Cancer Patients
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
- Prostate Cancer
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
Arm | Description | Assigned 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. |
|
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. |
|
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. |
|
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. |
|
More Details
- Status
- Completed
- Sponsor
- Rapamycin Holdings, Inc. dba Emtora Biosciences
Study Contact
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.