Clinical trial NCT03618355: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Lead sponsor: Rapamycin Holdings Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cancer Insight, LLC
First posted: 2018-08-07
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: Inclusion Criteria:

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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

Primary outcomes:
measure: Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
timeFrame: After 4 weeks of treatment in each dosing cohort.
measure: Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
timeFrame: After completion of treatment, approximately 12 weeks, in each dosing cohort.
measure: Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
timeFrame: This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur at 1 year.
measure: Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
timeFrame: This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.
Secondary outcomes:
measure: Secondary Pharmacokinetics: AUC
timeFrame: 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.
measure: Secondary Pharmacokinetics: Exposure Trough Levels
timeFrame: Cohorts 3 and 4 PK analysis will occur during the first week of treatment.
measure: Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6
timeFrame: 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.
measure: Secondary Pharmacodynamics: mTOR inhibition upon initial dose
timeFrame: Cohorts 1 and 2 PD analysis will occur during the first week.
measure: Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing
timeFrame: Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
measure: Secondary Pharmacodynamics: mTOR inhibition during final week of treatment
timeFrame: Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.
measure: Secondary Immunologic Response: T cell phenotype individually
timeFrame: 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).
measure: Secondary Immunologic Response: T cell function individually
timeFrame: 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).
measure: Secondary Immunologic Response: T cell phenotype within each dosing cohort
timeFrame: 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).
measure: Secondary Immunologic Response: T cell function within each dosing cohort
timeFrame: 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).
measure: Secondary Immunologic Response: T cell phenotype overall study-wide
timeFrame: 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).
measure: Secondary Immunologic Response: T cell function overall study-wide
timeFrame: 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).
measure: Secondary Quality of Life Analysis
timeFrame: Assessments performed baseline, after completion of therapy (approximately 12 weeks), and after 6 months.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
Study officials:
affiliation: Cancer Insight
name: George E Peoples, MD, FACS
role: STUDY_DIRECTOR
References: