Pharmacokinetic Food-effect Study of Abiraterone Acetate (AA) in Castration Resistant Prostate Cancer (ABIFOOD01)
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
AA Reduced dose-normal diet (A)
AA reduced dose-fat diet (B)
AA normal dose-fasting conditions (C)
Sponsored by

About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring pharmacokinetics, food-effect, fat diet, abiraterone acetate
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically or cytologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or with no small cell histology.
- At least one, but no more than two regimens of cytotoxic chemotherapy for metastatic castration-resistant prostate cancer. At least one regimen must have contained docetaxel.
- Men 18 years old or more.
- Criteria for progression according to the recommendations of the Prostate Cancer Working Group.
- Androgen deprivation present with testosterone levels <50 ng / dl or <2.0 nmol / l).
- ECOG (Eastern Cooperative Oncology Group) performance status <2.
- Adequate organ function
- Accept the use of barrier methods of contraception throughout the study
- Signature of informed consent to participate in the study consent.
Exclusion Criteria:
- Inability or unwillingness to swallow tablets.
- Known brain metastases
- Significant chronic gastrointestinal disorder with diarrhea as the main symptom (Crohn's disease, ulcerative colitis, malabsorption, or grade ≥ 2 diarrhea of any etiology at baseline).
- Local prostate surgery or intervention within 30 days prior to the first dose. Further, any clinically relevant sequel to surgery should be resolved before the 1st of cycle 1.
- Radiotherapy, chemotherapy or immunotherapy within 30 days before or single fraction of palliative radiotherapy within 14 days prior to the administration of the day 1of Cycle 1.
- Patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, heart failure Class III or IV of the New York Heart Association or cardiac ejection fraction <50%, active or symptomatic viral hepatitis, chronic liver failure, clinically significant adrenal or pituitary dysfunction. (Patients with hypertension controlled with drugs are allowed)
- Any acute toxicity due to chemotherapy and / or prior radiotherapy has not been resolved to ≤ grade 1 NCI CTCAE (version 4). Alopecia and grade 2 peripheral neuropathy induced by chemotherapy are allowed.
- Previous treatment with abiraterone acetate.
Sites / Locations
- Hospital Universitario Virgen del Rocío
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
AA Reduced dose-normal diet (A)
AA reduced dose-fat diet (B)
AA normal dose-fasting conditions (C)
Arm Description
Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a standard breakfast
Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a fat breakfast
Abiraterone acetate at approved dose of 1000 mg po daily in cycles of 28 days administered in fasting conditions
Outcomes
Primary Outcome Measures
Area under curve (AUC)
Area under curve at time t and infinite, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Peak Plasma Concentration (Cmax)
Peak Plasma Concentration (Cmax) of acetate administered at low doses with meals, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Time to reach peak plasma concentration (Tmax)
Time to reach peak plasma concentration (Tmax) of acetate administered at low doses with meals, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Secondary Outcome Measures
PSA (Prostate Specific Antigen) levels
Basal PSA levels and monitoring until disease progression
Response rate
Response rate according to RECIST 1.1
Pain intensity
Pain intensity measured by the Brief Pain Inventory-Short Form scale (BPI-SF)
Use of analgesics
Type of analgesics used for pain treatment.
Total daily dose of analgesics
Total daily dose of analgesics will be recorded.
Full Information
NCT ID
NCT02730975
First Posted
September 15, 2015
Last Updated
January 8, 2021
Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
1. Study Identification
Unique Protocol Identification Number
NCT02730975
Brief Title
Pharmacokinetic Food-effect Study of Abiraterone Acetate (AA) in Castration Resistant Prostate Cancer
Acronym
ABIFOOD01
Official Title
Pharmacokinetic Food-effect Study of Abiraterone Acetate (A.A) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
May 12, 2014 (Actual)
Primary Completion Date
October 10, 2020 (Actual)
Study Completion Date
October 10, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
ABIFOOD study is a randomized open-labelled, phase I study to evaluate food effect in the pharmacokinetic parameters of abiraterone acetate (AA) at reduced doses, versus AA in fasting conditions at conventional doses, in castration resistant prostate cancer (mCRPC) patients who have progressed to docetaxel.
Detailed Description
Abiraterone acetate (AA) has been approved for the treatment of mCRPC after docetaxel progression at doses of 1.000 mg per day taken in fasting conditions. However, it has been described both the significant food-effect on bioavailability up to 5 to 10 times folder increase depending on the fat content of the diet. These data come from the analysis of a small number of patients in phase I studies conducted in the early stages of drug development and some exploratory study in healthy subjects. There is not prospective randomized study that has analyzed the real impact of the normal diet in the bioavailability of the drug (not a fatty diet like has been used in initial studies).
Given the particular epidemiology of mCRPC (relatively frequent pathology), and taking into account recent data which indicates positive results of AA treatment in patients who had not previously received chemotherapy, a significant use of this drug is anticipated in the uro-oncology community in the coming years.
The precise definition of dose according to the food-effect on bioavailability may be critical not only from a purely medical perspective and / or pharmacological but even for its socioeconomic impact in our health system.
The hypothesis for this study is to prove that AA administered in reduced doses with standard diet presents a suitable pharmacokinetic profile which would achieve therapeutic levels in blood, so that regimens lower than currently approved in association with food can be used in future studies on efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
pharmacokinetics, food-effect, fat diet, abiraterone acetate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AA Reduced dose-normal diet (A)
Arm Type
Experimental
Arm Description
Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a standard breakfast
Arm Title
AA reduced dose-fat diet (B)
Arm Type
Experimental
Arm Description
Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a fat breakfast
Arm Title
AA normal dose-fasting conditions (C)
Arm Type
Active Comparator
Arm Description
Abiraterone acetate at approved dose of 1000 mg po daily in cycles of 28 days administered in fasting conditions
Intervention Type
Drug
Intervention Name(s)
AA Reduced dose-normal diet (A)
Other Intervention Name(s)
Abiraterone acetate 250 mg normal diet
Intervention Description
Cycles of 28 days length of AA at reduced doses (250 mg) administered with a pre-defined normal diet, described with specific caloric and fat content.
Intervention Type
Drug
Intervention Name(s)
AA reduced dose-fat diet (B)
Other Intervention Name(s)
Abiraterone acetate 250 mg fat- diet
Intervention Description
Cycles of 28 days length of AA at reduced doses (250 mg) administered with a pre-defined fat diet, described with specific caloric and fat content.
Intervention Type
Drug
Intervention Name(s)
AA normal dose-fasting conditions (C)
Other Intervention Name(s)
Abiraterone acetate 1000 mg fasting conditions
Intervention Description
Cycles of 28 days length of AA at approved doses (1000 mg) administered in fasting conditions.
Primary Outcome Measure Information:
Title
Area under curve (AUC)
Description
Area under curve at time t and infinite, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Time Frame
1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose in day 1 of cycle 1 (28 days long) , day 10-14 of cycle 1 and day 1 of cycle 5(28 days long)
Title
Peak Plasma Concentration (Cmax)
Description
Peak Plasma Concentration (Cmax) of acetate administered at low doses with meals, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Time Frame
1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose in day 1 of cycle 1 (28 days long) , day 10-14 of cycle 1 and day 1 of cycle 5(28 days long)
Title
Time to reach peak plasma concentration (Tmax)
Description
Time to reach peak plasma concentration (Tmax) of acetate administered at low doses with meals, compared with abiraterone acetate administered a standard dose fasting in the times specified: 1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose
Time Frame
1, 2, 3, 4, 5, 6, 8, 12, y 24 hours post dose in day 1 of cycle 1 (28 days long) , day 10-14 of cycle 1 and day 1 of cycle 5(28 days long)
Secondary Outcome Measure Information:
Title
PSA (Prostate Specific Antigen) levels
Description
Basal PSA levels and monitoring until disease progression
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Title
Response rate
Description
Response rate according to RECIST 1.1
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Title
Pain intensity
Description
Pain intensity measured by the Brief Pain Inventory-Short Form scale (BPI-SF)
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Title
Use of analgesics
Description
Type of analgesics used for pain treatment.
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Title
Total daily dose of analgesics
Description
Total daily dose of analgesics will be recorded.
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with histologically or cytologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or with no small cell histology.
At least one, but no more than two regimens of cytotoxic chemotherapy for metastatic castration-resistant prostate cancer. At least one regimen must have contained docetaxel.
Men 18 years old or more.
Criteria for progression according to the recommendations of the Prostate Cancer Working Group.
Androgen deprivation present with testosterone levels <50 ng / dl or <2.0 nmol / l).
ECOG (Eastern Cooperative Oncology Group) performance status <2.
Adequate organ function
Accept the use of barrier methods of contraception throughout the study
Signature of informed consent to participate in the study consent.
Exclusion Criteria:
Inability or unwillingness to swallow tablets.
Known brain metastases
Significant chronic gastrointestinal disorder with diarrhea as the main symptom (Crohn's disease, ulcerative colitis, malabsorption, or grade ≥ 2 diarrhea of any etiology at baseline).
Local prostate surgery or intervention within 30 days prior to the first dose. Further, any clinically relevant sequel to surgery should be resolved before the 1st of cycle 1.
Radiotherapy, chemotherapy or immunotherapy within 30 days before or single fraction of palliative radiotherapy within 14 days prior to the administration of the day 1of Cycle 1.
Patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, heart failure Class III or IV of the New York Heart Association or cardiac ejection fraction <50%, active or symptomatic viral hepatitis, chronic liver failure, clinically significant adrenal or pituitary dysfunction. (Patients with hypertension controlled with drugs are allowed)
Any acute toxicity due to chemotherapy and / or prior radiotherapy has not been resolved to ≤ grade 1 NCI CTCAE (version 4). Alopecia and grade 2 peripheral neuropathy induced by chemotherapy are allowed.
Previous treatment with abiraterone acetate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ignacio Durán Martínez, MD-PhD
Organizational Affiliation
Hospital Universitario Virgen del Rocío, Seville, Spain
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Clara Rosso Fernández, MD-PhD
Organizational Affiliation
Hospital Universitario Virgen del Rocío, Seville, Spain
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Virgen del Rocío
City
Seville
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Pharmacokinetic Food-effect Study of Abiraterone Acetate (AA) in Castration Resistant Prostate Cancer
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