Trial of eRapa in Prostate Cancer Patients

Rapamycin Holdings (Emtora Biosciences)

Status and phase: Completed; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: eRapa (encapsulated rapamycin)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03618355

RHI-P01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 4 patient groups

Cohort 1: 0.5 mg weekly

Experimental group

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.

Treatment:

Drug: eRapa (encapsulated rapamycin)

Cohort 2: 1 mg weekly

Experimental group

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.

Treatment:

Drug: eRapa (encapsulated rapamycin)

Cohort 3: 0.5 mg daily

Experimental group

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.

Treatment:

Drug: eRapa (encapsulated rapamycin)

Cohort 4: 1 mg daily

Experimental group

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.

Treatment:

Drug: eRapa (encapsulated rapamycin)