Pharmacokinetic Food-effect Study of Abiraterone Acetate (AA) in Castration Resistant Prostate Cancer

NCT ID: NCT02730975

Last Updated: 2021-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-12
• Study Completion Date: 2020-10-10

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AA Reduced dose-normal diet (A)

Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a standard breakfast

Group Type: EXPERIMENTAL

AA Reduced dose-normal diet (A)

Intervention Type: DRUG

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.

AA reduced dose-fat diet (B)

Abiraterone acetate at reduced dose of 250 mg po daily in cycles of 28 days administered with a fat breakfast

Group Type: EXPERIMENTAL

AA reduced dose-fat diet (B)

Intervention Type: DRUG

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.

AA normal dose-fasting conditions (C)

Abiraterone acetate at approved dose of 1000 mg po daily in cycles of 28 days administered in fasting conditions

Group Type: ACTIVE_COMPARATOR

AA normal dose-fasting conditions (C)

Intervention Type: DRUG

Cycles of 28 days length of AA at approved doses (1000 mg) administered in fasting conditions.

Interventions

AA Reduced dose-normal diet (A)

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

AA reduced dose-fat diet (B)

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

AA normal dose-fasting conditions (C)

Cycles of 28 days length of AA at approved doses (1000 mg) administered in fasting conditions.

Intervention Type: DRUG

Other Intervention Names

Abiraterone acetate 250 mg normal diet; Abiraterone acetate 250 mg fat- diet; Abiraterone acetate 1000 mg fasting conditions

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ignacio Durán Martínez, MD-PhD

Role: STUDY_DIRECTOR

Hospital Universitario Virgen del Rocío, Seville, Spain

Clara Rosso Fernández, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Virgen del Rocío, Seville, Spain

Locations

Hospital Universitario Virgen del Rocío

Seville, , Spain

Countries

Spain

Other Identifiers

2012-003226-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ABIFOOD01

Identifier Type: -

Identifier Source: org_study_id