Castration Levels of TestosteroneNCT02228265
Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide
An observational study of Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by OHSU Knight Cancer Institute at 3 sites in United States.
Trial summary
This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Adenocarcinoma
- What is being tested?
- Cytology Specimen Collection Procedure, Enzalutamide and Laboratory Biomarker Analysis
- How many people
- 41 participants
- Where
- 3 sitesUnited States
- Study dates
- 12 Mar 2013to 27 Feb 2020
- Phase
- Observational
- 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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with prostate cancer treated at Oregon Health and Science University Knight Cancer Institute
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
- Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
- Willingness to undergo a tumor biopsy at baseline and at disease progression
- Serum testosterone level < 50 ng/dL at screening
- Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:
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- PSA progression defined by a minimum of three rising PSA levels with an interval of >= 1 week between each determination; the PSA value at screening should be >= 2 ug/L (2 ng/ml)
- Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Bone disease progression defined by two or more new lesions on bone scan
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)
- Willing and able to give informed consent
- A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for < 3 months require only a 2 week washout period prior to first dose of study drug
Who cannot join
- Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
- Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
- Platelet count < 75,000/uL
- Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT > 1.5 times the institutional upper limit of normal (ULN)
- Structurally unstable bone lesions suggesting impending fracture
- Previous treatment with MDV3100, ARN-509, or BMS-641988
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- Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies
- Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment
- A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
OHSU Knight Cancer Institute
Portland, Oregon, 97239
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
About this study
Official title: Identifying Mechanisms of Resistance to Enzalutamide (MDV3100) Treatment in Men With Castration-Resistant Prostate Cancer
This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (</>= 50% decline) at 12 weeks versus (vs.) baseline.
SECONDARY OBJECTIVES:
- To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause).
II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression.
III. To identify molecular features and cellular pathways present in tumors from men with metastatic castrate-resistant prostate cancer (CRPC) that are progressing despite enzalutamide treatment.
IV. To explore correlation between baseline molecular features and pathways and objective response.
- To assess the correlations between the baseline molecular features and pathways and degree of PSA decline at 12 weeks and maximal PSA decline observed while on study.
VI. To assess the correlations between the baseline molecular features and time on treatment.
TERTIARY OBJECTIVES:
- To assess correlations between cell-free deoxyribonucleic acid (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples.
II. To assess correlations between cfDNA molecular features and endpoints in the primary and secondary objectives listed above.
III. To explore correlations with baseline molecular features and tissue histology.
IV. To explore correlations with baseline tissue histology and PSA change, time to PSA progression, time on treatment, progression-free survival, and overall survival.
OUTLINE:
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide, and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
After completion of study, patients are followed up every 12 weeks.
- Conditions
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Adenocarcinoma, PSA Progression, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer
- Being tested
- Cytology Specimen Collection Procedure, Enzalutamide, Laboratory Biomarker Analysis
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytology Specimen Collection ProcedureOther
Also called Cytologic Sampling
Undergo blood and tissue collection
EnzalutamideDrug
Also called ASP9785, MDV3100, Xtandi
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Ancillary-Correlative (genetic analysis) | Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing. Receives: Other: Cytology Specimen Collection Procedure; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment
Will be reported with 95% exact confidence interval.
Measured: Within 12 weeks
Secondary outcomes (9)
Degree of PSA decline
Simple linear regression will be used to assess the association between molecular biomarker predictors and the continuous endpoints. Logarithm transformation or other forms of transformation may be conducted to the continuous endpoints to address the skewedness of the distributions if necessary.
Measured: 12 weeks
Disease-specific survival
Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% versus patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks versus those who had not.
Measured: Time from day 1 of the study drug to date of death from prostate cancer, assessed up to 4 years
Maximal PSA decline observed while on study
Simple linear regression will be used to assess the association between molecular biomarker predictors and the continuous endpoints. Logarithm transformation or other forms of transformation may be conducted to the continuous endpoints to address the skewedness of the distributions if necessary.
Measured: Up to 4 years
Molecular features
Will assess correlations between the baseline molecular features and time on treatment.
Measured: Up to 4 years
Objective response
Will be summarized using the estimated proportion and 95% confidence interval. Simple logistic regression model will be used to assess the association between molecular biomarker predictors and these binary secondary endpoints.
Measured: Up to 4 years
Overall survival
Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% versus patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks versus those who had not.
Measured: Time from day 1 of study drug treatment to date of death from any cause, assessed up to 4 years
Progression for a subgroup of patients who have metastatic castration resistant prostate cancer and have received enzalutamide treatment
Will be summarized using the estimated proportion and 95% confidence interval. Simple logistic regression model will be used to assess the association between molecular biomarker predictors and these binary secondary endpoints.
Measured: Up to 4 years
Progression-free survival
Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% versus patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks versus those who had not.
Measured: Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 4 years
Time to PSA progression
Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% versus patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks versus those who had not.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study start12 Mar 2013
- Primary completion1 Oct 2019
- Study completion27 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration Levels of TestosteroneStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, Oregon Health and Science University
- Responsible party
- Principal investigator, Tom Beer, OHSU Knight Cancer Institute
- Investigators
- Joshi Alumkal, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228265
- Sponsor's protocol ID
- IRB00009259
- Other IDs
- NCI-2014-01438, MR00046920, IRB00009259
- Status last verified
- Sep 2020
- First submitted
- 25 Aug 2014
- Last updated
- 28 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identifying Mechanisms of Resistance to Enzalutamide (MDV3100) Treatment in Men With Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02228265
- Acronym / sponsor ID
- IRB00009259
- Conditions
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Adenocarcinoma, PSA Progression, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- United States Department of Defense, Oregon Health and Science University
- Study start
- 12 Mar 2013 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 29 Aug 2014 (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.
This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.
Detailed description
PRIMARY OBJECTIVES:
- To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (</>= 50% decline) at 12 weeks versus (vs.) baseline.
SECONDARY OBJECTIVES:
- To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause).
II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression.
III. To identify molecular features and cellular pathways present in tumors from men with metastatic castrate-resistant prostate cancer (CRPC) that are progressing despite enzalutamide treatment.
IV. To explore correlation between baseline molecular features and pathways and objective response.
- To assess the correlations between the baseline molecular features and pathways and degree of PSA decline at 12 weeks and maximal PSA decline observed while on study.
VI. To assess the correlations between the baseline molecular features and time on treatment.
TERTIARY OBJECTIVES:
- To assess correlations between cell-free deoxyribonucleic acid (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples.
II. To assess correlations between cfDNA molecular features and endpoints in the primary and secondary objectives listed above.
III. To explore correlations with baseline molecular features and tissue histology.
IV. To explore correlations with baseline tissue histology and PSA change, time to PSA progression, time on treatment, progression-free survival, and overall survival.
OUTLINE:
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide, and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
After completion of study, patients are followed up every 12 weeks.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ancillary-Correlative (genetic analysis) | – | Other: Cytology Specimen Collection Procedure, Drug: Enzalutamide, Other: Laboratory Biomarker AnalysisPatients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with prostate cancer treated at Oregon Health and Science University Knight Cancer Institute
Key inclusion criteria (13 listed)
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
- Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
- Willingness to undergo a tumor biopsy at baseline and at disease progression
- Serum testosterone level < 50 ng/dL at screening
Key exclusion criteria (9 listed)
- Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
- Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
- Platelet count < 75,000/uL
- Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT > 1.5 times the institutional upper limit of normal (ULN)
- Structurally unstable bone lesions suggesting impending fracture
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 |
|---|---|---|
| Cytology Specimen Collection ProcedureAlso: Cytologic SamplingUndergo blood and tissue collection | Other | Ancillary-Correlative (genetic analysis) |
| EnzalutamideAlso: ASP9785, MDV3100, XtandiGiven PO | Drug | Ancillary-Correlative (genetic analysis) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Ancillary-Correlative (genetic analysis) |
Primary outcome
PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment
Time frame: Within 12 weeks
Will be reported with 95% exact confidence interval.
9 secondary outcomes
Degree of PSA decline
Time frame: 12 weeks
Disease-specific survival
Time frame: Time from day 1 of the study drug to date of death from prostate cancer, assessed up to 4 years
Maximal PSA decline observed while on study
Time frame: Up to 4 years
Molecular features
Time frame: Up to 4 years
Objective response
Time frame: Up to 4 years
Overall survival
Time frame: Time from day 1 of study drug treatment to date of death from any cause, assessed up to 4 years
Progression for a subgroup of patients who have metastatic castration resistant prostate cancer and have received enzalutamide treatment
Time frame: Up to 4 years
Progression-free survival
Time frame: Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 4 years
Time to PSA progression
Time frame: Up to 4 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 28 Sep 2020.
Related trials for Castration Levels of Testosterone
RecruitingPhase 3
Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
Castration Levels of Testosterone, Metastatic Prostatic Adenocarcinoma
Active, not recruitingPhase 2
Abiraterone Acetate and Antiandrogen Therapy With or Without Cabazitaxel and Prednisone in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer Previously Treated With Docetaxel
Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma
Active, not recruitingPhase 2
Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma
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.
Joshi Alumkal principal investigator
OHSU Knight Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by OHSU Knight Cancer Institute at 3 sites in United States.
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 13 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 28 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment (time frame: Within 12 weeks). 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 28 Sep 2020.