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A Safety and Feasibility Study of Mitotane in Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Mitotane
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Biopsy-proven prostate cancer OR a clinical picture consistent with metastatic prostate cancer with high levels of serum PSA (>20ng/ml)
  • Progressed on docetaxel chemotherapy after a minimum of 3 cycles and/or stopped treatment because of toxicity. Patients may have had previous mitoxantrone, either before or after docetaxel treatment
  • Response to a minimum of a 50% fall in PSA maintained for 4 weeks and then progressed through abiraterone treatment
  • At least 2 consecutive rising PSAs measured at least 1 week apart . Patients must have ceased abiraterone at least 1 week prior.
  • Serum PSA > 10 ng/ml
  • ECOG performance status </= 1 (Karnofsky >/=60%)

  • Normal organ and marrow function as defined:

    • Absolute neutrophils count ≥ 1,500/uL
    • platelets ≥100,000/uL
    • total bilirubin ≤1.5 X institutional ULN
    • AST(SGOT)/ALT(SGPT) ≤ 2 X institutional ULN
    • creatinine ≤ 1.5 X institutional ULN
  • Men must agree to use adequate contraception prior to study entry
  • Life expectancy > 3 months
  • CRPC documented by PSA increase despite having: a) orchidectomy OR b) continuous LHRH agonist treatment. This should be documented by a baseline serum testosterone suppression (<1.75 nmol/L)

Exclusion Criteria:

  • Prior anticancer treatment with Mitotane
  • May not be receiving any other investigational or anticancer agents while on study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, poorly controlled diabetes mellitus, clinically significant or untreated ophthalmologic (e.g. Sjogrens etc.) or gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis) or psychiatric illness/social situations that would limit compliance with study requirements
  • Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
  • Radiotherapy within the past 4 weeks
  • Pre-existing pituitary or adrenal dysfunction
  • Patients on spironolactone as this may interfere with the action of mitotane
  • Patients on warfarin as mitotane may unpredictably interfere with INR measurements

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm

Arm Description

Mitotane will be administered on an outpatient or inpatient basis.

Outcomes

Primary Outcome Measures

The Primary Endpoint is the Proportion of Patients Maintained on Mitotane After 12 Consecutive Weeks of Therapy. A Positive Outcome Would be Seeing 50% or More Patients Maintained on Therapy. Secondary Endpoint Include Proportion of Adverse Events

Secondary Outcome Measures

Prostate Specific Antigen (PSA) Response Rate
Continue increase of serum PSA beyond 8 weeks indicate PSA progression. Response and progression will be primarily evaluated in this study using PSA response criteria from the Prostate Cancer Working Group 2. Criteria used to define response include: at least a 50% decline in PSA, confirmed by a second measurement ≥4 weeks later. PSA progression is defined by a >25% increase from baseline in patients whose PSA did not decrease, and of 50% from the nadir value in patients whose PSA decreased. This increase in PSA must be >5 ng/ml, and confirmed by a second measurement, at least 1 week later; PSA nadir is defined as the minimum PSA value that was confirmed by a second measurement. PSA progression free survival is defined as the time between the randomization date and the date of PSA progression or the date of death due to prostate cancer, whichever occurs first.

Full Information

First Posted
January 28, 2014
Last Updated
November 11, 2015
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT02057237
Brief Title
A Safety and Feasibility Study of Mitotane in Prostate Cancer
Official Title
A Safety and Feasibility Study of Mitotane in Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of this study is to assess the feasibility of treating patients with metastatic castration resistant prostate cancer with mitotane. Secondary objectives are to assess safety and tolerability as well as response rate of therapy To assess the toxicity of Mitotane in men with HRPC To assess the relationship between baseline serum adrenal androgens and their response to Mitotane
Detailed Description
All patients will undergo pre-study assessment for symptoms, performance status, ECG, CT abdomen/pelvis, Bone scan, Complete blood count tests(hematology) , Biochemistry tests like serum electrolytes, liver function tests, coagulation profile, testosterone and PSA tests. Mitotane will be administered 1.5g daily escalation to maximum of 5 g daily then adjusted according to serum levels and tolerability Physical examinations, hematology, biochemistry tests, and toxicity evaluations will be measured throughout patients on protocol treatment Mitotane serum level will be analyzed every second cycle Research bloods include; ACTH, cortisol, deoxycorticosterone, aldosterone, corticosterone, and testosterone, androstenedione, dehydroepiandrostenedione (DHEA), DHEA sulfate (DHEA-S) and estradiol will be collected only in cycle 1,3 and 5

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
single arm
Arm Type
Experimental
Arm Description
Mitotane will be administered on an outpatient or inpatient basis.
Intervention Type
Drug
Intervention Name(s)
Mitotane
Other Intervention Name(s)
Lysodren
Intervention Description
Mitotane will be administered at a starting dose of 1.5 g/day and increased in case of good gastrointestinal tolerance every 3rd day by 0.5 g up to a maximal dose of 5.0 g and then adjusted according to blood concentrations monthly and tolerability, up to a maximum of 10g daily
Primary Outcome Measure Information:
Title
The Primary Endpoint is the Proportion of Patients Maintained on Mitotane After 12 Consecutive Weeks of Therapy. A Positive Outcome Would be Seeing 50% or More Patients Maintained on Therapy. Secondary Endpoint Include Proportion of Adverse Events
Time Frame
maintain 50% of the patients on Mitotane at the 12 week mark
Secondary Outcome Measure Information:
Title
Prostate Specific Antigen (PSA) Response Rate
Description
Continue increase of serum PSA beyond 8 weeks indicate PSA progression. Response and progression will be primarily evaluated in this study using PSA response criteria from the Prostate Cancer Working Group 2. Criteria used to define response include: at least a 50% decline in PSA, confirmed by a second measurement ≥4 weeks later. PSA progression is defined by a >25% increase from baseline in patients whose PSA did not decrease, and of 50% from the nadir value in patients whose PSA decreased. This increase in PSA must be >5 ng/ml, and confirmed by a second measurement, at least 1 week later; PSA nadir is defined as the minimum PSA value that was confirmed by a second measurement. PSA progression free survival is defined as the time between the randomization date and the date of PSA progression or the date of death due to prostate cancer, whichever occurs first.
Time Frame
PSA progression free survival and excessive toxicity. Plan to keep the patients on Mitotane for atleast 8 weeks, despite increasing level of PSA as other trials shown early increase in PSA followed by a subsequent decline.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy-proven prostate cancer OR a clinical picture consistent with metastatic prostate cancer with high levels of serum PSA (>20ng/ml) Progressed on docetaxel chemotherapy after a minimum of 3 cycles and/or stopped treatment because of toxicity. Patients may have had previous mitoxantrone, either before or after docetaxel treatment Response to a minimum of a 50% fall in PSA maintained for 4 weeks and then progressed through abiraterone treatment At least 2 consecutive rising PSAs measured at least 1 week apart . Patients must have ceased abiraterone at least 1 week prior. Serum PSA > 10 ng/ml ECOG performance status </= 1 (Karnofsky >/=60%) Normal organ and marrow function as defined: Absolute neutrophils count ≥ 1,500/uL platelets ≥100,000/uL total bilirubin ≤1.5 X institutional ULN AST(SGOT)/ALT(SGPT) ≤ 2 X institutional ULN creatinine ≤ 1.5 X institutional ULN Men must agree to use adequate contraception prior to study entry Life expectancy > 3 months CRPC documented by PSA increase despite having: a) orchidectomy OR b) continuous LHRH agonist treatment. This should be documented by a baseline serum testosterone suppression (<1.75 nmol/L) Exclusion Criteria: Prior anticancer treatment with Mitotane May not be receiving any other investigational or anticancer agents while on study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, poorly controlled diabetes mellitus, clinically significant or untreated ophthalmologic (e.g. Sjogrens etc.) or gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis) or psychiatric illness/social situations that would limit compliance with study requirements Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin Radiotherapy within the past 4 weeks Pre-existing pituitary or adrenal dysfunction Patients on spironolactone as this may interfere with the action of mitotane Patients on warfarin as mitotane may unpredictably interfere with INR measurements
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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A Safety and Feasibility Study of Mitotane in Prostate Cancer

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