Pharmacogenetic StudyABIGENENCT01858441
Pharmacogenetic Study in Castration-resistant Prostate Cancer Patients Treated With Abiraterone Acetate
A study testing Abiraterone Acetate in people with Pharmacogenetic Study, run by Centre Antoine Lacassagne at 1 site in France.
Trial summary
Prostate cancer is the 2nd leading cause of mortality in men in developed countries. For metastatic prostate cancer patients, the 1st-line treatment relies on hormone therapy. However, the efficacy of androgen deprivation therapy remains limited in time and most patients eventually develop castration-resistant… Read more about this study
- Who is it for?
- Ages 18 to 90 years, men only
- Conditions the study is for
- Pharmacogenetic Study
- What is being tested?
- Abiraterone Acetate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2013to 3 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years. Histologically confirmed prostate adenocarcinoma. ECOG ≤ 2. Evidence of metastatic disease by the presence of documented locoregional or distant metastases on CT scan of the abdomen and/or pelvis, or bone scintigraphy.
- Patients who have had disease progression during or after prior docetaxel chemotherapy regimen, defined as:
- Progressive measurable disease : At least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed -or- the appearance of one or more new measurable lesions as assessed by CT scan. Soft tissue disease progression defined by modified RECIST 1.1 criteria (baseline lymph node size must be ≥ 2.0 cm to be considered target or evaluable lesion).
- OR Bone Scan Progression: appearance of 2 or more new lesions on bone scan. OR Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. A minimum starting value of 2.0 ng/mL is required for study entry.
- NOTE: Androgen ablative therapy may have included either medical or surgical castration.
- At least one prior chemotherapy regimen of docetaxel. At least 28 days had to have elapsed between the withdrawal of antiandrogens and enrolment, except LH-RH agonist therapy that must be continued throughout this study for patients who were already treated by it.
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- Hormonal castration confirmed biologically (testosterone < 0.5 ng/ml). Patient with adequate organ function10. Patient able to swallow abiraterone acetate whole as a tablet.
- Information delivered to patient and informed consent signed by the patient or legal representative.
- Patient affiliated with a health insurance system.
Who cannot join
- Patients already treated with abiraterone acetate. Known hypersensitivity or allergy to abiraterone or any of the excipients Patients suffering from severe or moderate hepatic impairment (Child-Pugh Class B or C), active or symptomatic viral hepatitis or renal impairment.
- Any radiation within 28 days prior to study entry. Patient with central nervous system (CNS) metastasis or with history of CNS metastasis.
- Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma, within the past 5 years.
- Treatment on another therapeutic clinical trial within 28 days before enrolment Prior treatment with novel hormonal agents including enzalutamide, orteronel, ARN509, EPI100 and novel non hormonal treatments including cabozantinib, alpharadin.
- Patients with uncontrolled hypertension, heart disease clinically significant (such as myocardial infarction or recent arterial thrombotic events, severe or unstable angina, heart failure class III-IV NYHA (appendix 5) or with a measurement of the cardiac ejection fraction <50%), within 6 months of randomization.
- Any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
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- Permanent contraindication to corticosteroids. Patients who have partners of childbearing potential who are not willing to use refusing 2 methods of birth control with adequate barrier protection during the study and for 13 weeks after last study drung administration.
- Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol.
- Patient enables to give informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Prostate cancer is the 2nd leading cause of mortality in men in developed countries. For metastatic prostate cancer patients, the 1st-line treatment relies on hormone therapy. However, the efficacy of androgen deprivation therapy remains limited in time and most patients eventually develop castration-resistant prostate cancer (CRPC), while remaining androgen-dependent.
Docetaxel is currently the standard of care for metastatic CPRC. It has been shown that testosterone levels within metastatic tumoral tissue from men receiving hormone therapy were significantly higher than those from primitive tumors of untreated prostate cancers. Among the mechanistic explanations for this observation, it has been shown that CYP17A1, a key enzyme in de novo steroid synthesis localized in testis and adrenal gland, is up-regulated in CRPC metastases. The existence of de novo CYP17A1-dependent androgen biosynthesis at the tumor level has supported the development of novel antiandrogens, including abiraterone acetate (AA), an irreversible CYP17A1 inhibitor. Based on a placebo-controlled phase III trial, demonstrating that abiraterone prolonged overall survival (14.8 vs 10.9 months) and increased PSA response rate (29% vs 6%) in patients with metastatic CRPC who previously received docetaxel, AA was recently approved by the FDA and French Health Authorities. AA is well-tolerated and main toxicities are urinary tract infections (2%) and a syndrome of secondary mineralocorticoid excess characterized by fluid overload, hypertension and hypokaliema (1% to 4% of grade 3-4).
Read more
Almost concomitantly, a novel taxane-class cytotoxic agent, cabazitaxel, has proven efficacy in CRPC treatment after failure to docetaxel, and has recently been approved by the FDA and French Health Authority. Although cabazitaxel exhibits a less favorable toxicity profile, this precise context creates a need to dispose of objective individual criteria so as to orientate patients to treatment towards AA or towards cabazitaxel. To this purpose, several approaches are of potential interest for identifying good candidates for a treatment by AA: tumor-specific TMPRSS2-ERG gene fusion measurement, circulating tumor cell analysis, tumoral CYP17A1 expression, analysis of splicing forms of the androgen receptor. However, the clinical relevance of these potential predictive factors remains to be established in this setting.
Pharmacogenetics examines germinal gene polymorphisms likely to influence the pharmacodynamics of anticancer agents. Encouraging results have recently been reported by our group for irinotecan pharmacogenetics with concrete possibilities of individual dose adaptations, and very recently by other investigators for sunitinib pharmacogenetics. Concerning AA, one can hypothesize that tumors with elevated CYP17A1 expression will be more likely to respond better to AA. This hypothesis is indirectly supported by the observation that in CPRC patients receiving AA, PSA-based response is higher in patients with elevated pre-treatment blood concentration of DHEA and androstenedione.
The CYP17A1 gene presents numerous single nucleotide polymorphisms (SNPs), whose frequencies of rare alleles are at least 12%. Their functional impact has been suggested for nine of them, which were linked either to the risk of developing prostate cancer or to survival of prostate cancer patients. So far, no study has examined the links between these polymorphisms and the efficacy of a CYP17A1 inhibitor. Also, relationships with the efficacy of androgen deprivation therapy have recently been reported for SNPs of genes involved in the membrane-transport testosterone and dehydroepiandrosterone, namely SLCO2B1 and SLCO1B3. One can make the hypothesis that gene polymorphisms of these transporters may play a role for the intratumoral concentration of testosterone locally-produced through the mediation of CYP17A1 activity.
To resume, two second-line treatments of metastatic CRPC cancers are currently available, thus is raising the question in practice of which treatment is more appropriate for a given patient. Herein, the present study proposes an original pharmacogenetic approach in order to highlight a relationship between AA activity and patient's genetic profile. Ultimately, this could reveal evidences of genetic predispositions for potentially good responders to AA treatment.
- Conditions
- Pharmacogenetic Study
- Being tested
- Abiraterone Acetate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abiraterone AcetateDrug
| Study group | Role | What they receive |
|---|---|---|
| Abiraterone Acetate | Other | Not described Receives: Drug: Abiraterone Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival
The primary objective will be to investigate the relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival. Such relationships will take into account relevant histo-prognostic factors of metastatic CRPC cancers (clinical staging, pre-treatment PSA, Gleason score) and treatment compliance.
Measured: up to 3 years
Secondary outcomes (4)
PSA response-rate will be defined as a decrease of 50% in the PSA concentration from pre-treatment baseline PSA value, confirmed after 4 weeks by an additional PSA evaluation.
Measured: up to 3 years
Symptomatic or clinical progression
Symptomatic or clinical progression will be defined as the time from start of therapy to the first sign of progression defined by one of the following:
Pain progression - Worsening of pain due to metastatic bone disease feel by the patient, and according the investigator's physical examination, Development of a skeletal related event (SRE) defined as pathologic fracture, spinal cord compression, palliative radiation to bone, or surgery to bone, General physical health deterioration Any increase in prednisone or prednisolone dose or a change to a more potent glucocorticoid such as dexamethasone, to treat prostate cancer related signs and symptoms, such as fatigue and pain are considered a disease progression event.
Measured: up to 3 years
Toxicity
All adverse events and serious adverse events will be recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 will be used (Appendix 3) to grade clinical and laboratory AEs.
Measured: up to 3 years
Histo-prognostic factors and treatment compliance
- Histo-prognostic factors of metastatic CRPC cancers including clinical staging, pre-treatment PSA, Gleason score will be collected at the inclusion visit.
- Treatment compliance will be evaluated by using a logbook: patients will be asked to keep track of their drug intake every day through it.
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study startApr 2013
- Primary completion6 Sep 2020
- Study completion3 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacogenetic StudyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Antoine Lacassagne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01858441
- Sponsor's protocol ID
- 2012-005036-28
- Acronym
- ABIGENE
- Status last verified
- Jul 2019
- First submitted
- 2 May 2013
- Last updated
- 4 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Study in Castration-resistant Prostate Cancer Patients Treated With Abiraterone Acetate
- ClinicalTrials.gov ID
- NCT01858441
- Acronym / sponsor ID
- ABIGENE / 2012-005036-28
- Conditions
- Pharmacogenetic Study
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Centre Antoine LacassagneUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- 6 Sep 2020 (actual)
- Study completion
- 3 Dec 2020 (actual)
- First posted
- 21 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prostate cancer is the 2nd leading cause of mortality in men in developed countries. For metastatic prostate cancer patients, the 1st-line treatment relies on hormone therapy. However, the efficacy of androgen deprivation therapy remains limited in time and most patients eventually develop castration-resistant prostate cancer (CRPC), while remaining androgen-dependent.
Docetaxel is currently the standard of care for metastatic CPRC. It has been shown that testosterone levels within metastatic tumoral tissue from men receiving hormone therapy were significantly higher than those from primitive tumors of untreated prostate cancers. Among the mechanistic explanations for this observation, it has been shown that CYP17A1, a key enzyme in de novo steroid synthesis localized in testis and adrenal gland, is up-regulated in CRPC metastases. The existence of de novo CYP17A1-dependent androgen biosynthesis at the tumor level has supported the development of novel antiandrogens, including abiraterone acetate (AA), an irreversible CYP17A1 inhibitor. Based on a placebo-controlled phase III trial, demonstrating that abiraterone prolonged overall survival (14.8 vs 10.9 months) and increased PSA response rate (29% vs 6%) in patients with metastatic CRPC who previously received docetaxel, AA was recently approved by the FDA and French Health Authorities. AA is well-tolerated and main toxicities are urinary tract infections (2%) and a syndrome of secondary mineralocorticoid excess characterized by fluid overload, hypertension and hypokaliema (1% to 4% of grade 3-4).
Almost concomitantly, a novel taxane-class cytotoxic agent, cabazitaxel, has proven efficacy in CRPC treatment after failure to docetaxel, and has recently been approved by the FDA and French Health Authority. Although cabazitaxel exhibits a less favorable toxicity profile, this precise context creates a need to dispose of objective individual criteria so as to orientate patients to treatment towards AA or towards cabazitaxel. To this purpose, several approaches are of potential interest for identifying good candidates for a treatment by AA: tumor-specific TMPRSS2-ERG gene fusion measurement, circulating tumor cell analysis, tumoral CYP17A1 expression, analysis of splicing forms of the androgen receptor. However, the clinical relevance of these potential predictive factors remains to be established in this setting.
Pharmacogenetics examines germinal gene polymorphisms likely to influence the pharmacodynamics of anticancer agents. Encouraging results have recently been reported by our group for irinotecan pharmacogenetics with concrete possibilities of individual dose adaptations, and very recently by other investigators for sunitinib pharmacogenetics. Concerning AA, one can hypothesize that tumors with elevated CYP17A1 expression will be more likely to respond better to AA. This hypothesis is indirectly supported by the observation that in CPRC patients receiving AA, PSA-based response is higher in patients with elevated pre-treatment blood concentration of DHEA and androstenedione.
The CYP17A1 gene presents numerous single nucleotide polymorphisms (SNPs), whose frequencies of rare alleles are at least 12%. Their functional impact has been suggested for nine of them, which were linked either to the risk of developing prostate cancer or to survival of prostate cancer patients. So far, no study has examined the links between these polymorphisms and the efficacy of a CYP17A1 inhibitor. Also, relationships with the efficacy of androgen deprivation therapy have recently been reported for SNPs of genes involved in the membrane-transport testosterone and dehydroepiandrosterone, namely SLCO2B1 and SLCO1B3. One can make the hypothesis that gene polymorphisms of these transporters may play a role for the intratumoral concentration of testosterone locally-produced through the mediation of CYP17A1 activity.
To resume, two second-line treatments of metastatic CRPC cancers are currently available, thus is raising the question in practice of which treatment is more appropriate for a given patient. Herein, the present study proposes an original pharmacogenetic approach in order to highlight a relationship between AA activity and patient's genetic profile. Ultimately, this could reveal evidences of genetic predispositions for potentially good responders to AA treatment.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Abiraterone Acetate | Other | Drug: Abiraterone Acetate |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age > 18 years. Histologically confirmed prostate adenocarcinoma. ECOG ≤ 2. Evidence of metastatic disease by the presence of documented locoregional or distant metastases on CT scan of the abdomen and/or pelvis, or bone scintigraphy.
- Patients who have had disease progression during or after prior docetaxel chemotherapy regimen, defined as:
- Progressive measurable disease : At least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed -or- the appearance of one or more new measurable lesions as assessed by CT scan. Soft tissue disease progression defined by modified RECIST 1.1 criteria (baseline lymph node size must be ≥ 2.0 cm to be considered target or evaluable lesion).
- OR Bone Scan Progression: appearance of 2 or more new lesions on bone scan. OR Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. A minimum starting value of 2.0 ng/mL is required for study entry.
- NOTE: Androgen ablative therapy may have included either medical or surgical castration.
Key exclusion criteria (9 listed)
- Patients already treated with abiraterone acetate. Known hypersensitivity or allergy to abiraterone or any of the excipients Patients suffering from severe or moderate hepatic impairment (Child-Pugh Class B or C), active or symptomatic viral hepatitis or renal impairment.
- Any radiation within 28 days prior to study entry. Patient with central nervous system (CNS) metastasis or with history of CNS metastasis.
- Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma, within the past 5 years.
- Treatment on another therapeutic clinical trial within 28 days before enrolment Prior treatment with novel hormonal agents including enzalutamide, orteronel, ARN509, EPI100 and novel non hormonal treatments including cabozantinib, alpharadin.
- Patients with uncontrolled hypertension, heart disease clinically significant (such as myocardial infarction or recent arterial thrombotic events, severe or unstable angina, heart failure class III-IV NYHA (appendix 5) or with a measurement of the cardiac ejection fraction <50%), within 6 months of randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abiraterone Acetate | Drug | Abiraterone Acetate |
Primary outcome
relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival
Time frame: up to 3 years
The primary objective will be to investigate the relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival. Such relationships will take into account relevant histo-prognostic factors of metastatic CRPC cancers (clinical staging, pre-treatment PSA, Gleason score) and treatment compliance.
4 secondary outcomes
PSA response-rate will be defined as a decrease of 50% in the PSA concentration from pre-treatment baseline PSA value, confirmed after 4 weeks by an additional PSA evaluation.
Time frame: up to 3 years
Symptomatic or clinical progression
Time frame: up to 3 years
Toxicity
Time frame: up to 3 years
Histo-prognostic factors and treatment compliance
Time frame: up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abiraterone Acetate in people with Pharmacogenetic Study, run by Centre Antoine Lacassagne at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival (time frame: up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2020; AzTrials last refreshed its copy on 6 Nov 2026.