NCT03618355

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at P25-P50 for phase_1 prostate-cancer

Timeline
Completed

Started Aug 2018

Shorter than P25 for phase_1 prostate-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 12, 2018

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 7, 2018

Completed
21 days until next milestone

Study Start

First participant enrolled

August 28, 2018

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 2, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 2, 2019

Completed
Last Updated

March 31, 2020

Status Verified

March 1, 2020

Enrollment Period

1.3 years

First QC Date

June 12, 2018

Last Update Submit

March 30, 2020

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (4)

  • Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)

    To analyze the overall safety of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

    After 4 weeks of treatment in each dosing cohort.

  • Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)

    To analyze the overall safety of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

    After completion of treatment, approximately 12 weeks, in each dosing cohort.

  • Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)

    To compare safety between dosing cohorts of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 at the 4 week time point.

    This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur at 1 year.

  • Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)

    To compare safety between dosing cohorts of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 at the 12 week time point.

    This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.

Secondary Outcomes (13)

  • Secondary Pharmacokinetics: AUC

    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.

  • Secondary Pharmacokinetics: Exposure Trough Levels

    Cohorts 3 and 4 PK analysis will occur during the first week of treatment.

  • Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6

    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.

  • Secondary Pharmacodynamics: mTOR inhibition upon initial dose

    Cohorts 1 and 2 PD analysis will occur during the first week.

  • Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing

    Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.

  • +8 more secondary outcomes

Study Arms (4)

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.

Drug: eRapa (encapsulated rapamycin)

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.

Drug: eRapa (encapsulated rapamycin)

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.

Drug: eRapa (encapsulated rapamycin)

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.

Drug: eRapa (encapsulated rapamycin)

Interventions

eRapa (encapsulated rapamycin)DRUG

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 weeklyCohort 2: 1 mg weeklyCohort 3: 0.5 mg dailyCohort 4: 1 mg daily

Eligibility Criteria

Age18 Years+
Sexmale(Gender-based eligibility)
Gender Eligibility DetailsPatient must have pathologically (histologically) proven diagnosis of prostate cancer with a Gleason score ≤7 (3+4) and already undergoing active surveillance.
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Study Officials

  • George E Peoples, MD, FACS

    Cancer Insight

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 12, 2018

First Posted

August 7, 2018

Study Start

August 28, 2018

Primary Completion

December 2, 2019

Study Completion

December 2, 2019

Last Updated

March 31, 2020

Record last verified: 2020-03

Data Sharing

IPD Sharing
Will not share

Locations

US(1)