Prostate CancerPREDYCNCT03979079
Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model
An observational study of Prostate Cancer, run by Institut Bergonié at 1 site in France.
Trial summary
Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- external beam radiation therapy
- Type of treatment
- Surgery or procedure
- How many people
- 2,384 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2010to 1 Jan 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Dataset of 2384 men included in three cohorts: University of Michigan, Ann Arbor, MI, USA (UM); Radiation Therapy Oncology Group (RTOG 9406); and William Beaumont Hospital, Detroit, MI, USA.
Who may be able to join
- clinically localized prostate cancer
- Clinical stage T1 to T4
- Node and metastasis negative
- Treated with external beam radiation therapy (RT).
Who cannot join
- Patients with baseline or planned hormonotherapy
Trial locations and contacts
1 site in 1 country.
About this study
Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure.
The two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework is particularly flexible to account for such data. Prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy can be monitored. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. The prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure based on a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. the aim of this research is to model prostate specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability can be expressed as a function of prostate-specific antigens concentration. Covariates in the survival model can include : hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process.
Read the detailed description
The two-stage modeling approach allows estimation of the regression coefficients in a time-dependent Cox model, while addressing the limitations with the knowledge of the true marker trajectory. In the first stage, the longitudinal process is modeled using a repeated measures component model, such as a random effects model. In the second stage, estimated characteristics of the longitudinal marker trajectory, such as slopes, are included as covariates in a survival model to assess their prognostic value.
Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo (MCMC) framework. We applied this model to assess the prognostic value of the prostate-specific antigens (PSA) profile (level and timing of the nadir; pre- and post-nadir slopes) as well as salvage hormonal treatment (HT) on the risk of clinical failure following external beam radiation therapy (EBRT) in the presence of confounding by indication. We first present the longitudinal hierarchical PSA model that we developed earlier. This model was particularly flexible since it allowed us to account for the presence of a random changepoint as well as the modeling of the residual variability as a function of the PSA concentration. We next extend the longitudinal model to a two-stage model by using estimated parameters of the longitudinal process as covariates in a Cox proportional hazards model to assess prognostic factors of clinical failure including baseline characteristics, PSA trajectory, and HT.
- Conditions
- Prostate Cancer
- Being tested
- external beam radiation therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
external beam radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinical Failure After Initiation of Radiotherapy
Clinical failure is defined as any of the following events following initiation of radiotherapy: distant metastases, nodal recurrence, or any palpable or biopsy-detected local recurrence three years after radiation; any local recurrence within three years of RT if the most previous PSA was>2 ng/ml; and death from prostate cancer.
Measured: within 10 years following initiation of radiotherapy
Secondary outcomes (1)
Number of Participants With Initiation of Salvage Therapy After Radiotherapy
Measured: within 10 years following initiation of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2019
- Study startJan 2010
- Primary completion1 Jan 2017
- Study completion1 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 2,384 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carine Bellera, PhD, Principal investigator, Institut Bergonié
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03979079
- Sponsor's protocol ID
- IB2010-PREDYC
- Acronym
- PREDYC
- Status last verified
- Dec 2020
- First submitted
- 4 Jun 2019
- Last updated
- 25 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bellera C, Proust-Lima C, Joseph L, Richaud P, Taylor J, Sandler H, Hanley J, Mathoulin-Pelissier S. A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication. Stat Methods Med Res. 2018 Apr;27(4):1271-1281. doi: 10.1177/0962280216660127. Epub 2016 Sep 1.
PubMed 27587597
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model
- ClinicalTrials.gov ID
- NCT03979079
- Acronym / sponsor ID
- PREDYC / IB2010-PREDYC
- Conditions
- Prostate Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,384 participants (actual)
- Lead sponsor
- Institut BergoniéUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- Jan 2010 (actual)
- Primary completion
- 1 Jan 2017 (actual)
- Study completion
- 1 Jan 2017 (actual)
- First posted
- 7 Jun 2019 (actual)
- Results
- Posted 21 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure.
The two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework is particularly flexible to account for such data. Prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy can be monitored. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. The prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure based on a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. the aim of this research is to model prostate specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability can be expressed as a function of prostate-specific antigens concentration. Covariates in the survival model can include : hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process.
Detailed description
The two-stage modeling approach allows estimation of the regression coefficients in a time-dependent Cox model, while addressing the limitations with the knowledge of the true marker trajectory. In the first stage, the longitudinal process is modeled using a repeated measures component model, such as a random effects model. In the second stage, estimated characteristics of the longitudinal marker trajectory, such as slopes, are included as covariates in a survival model to assess their prognostic value.
Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo (MCMC) framework. We applied this model to assess the prognostic value of the prostate-specific antigens (PSA) profile (level and timing of the nadir; pre- and post-nadir slopes) as well as salvage hormonal treatment (HT) on the risk of clinical failure following external beam radiation therapy (EBRT) in the presence of confounding by indication. We first present the longitudinal hierarchical PSA model that we developed earlier. This model was particularly flexible since it allowed us to account for the presence of a random changepoint as well as the modeling of the residual variability as a function of the PSA concentration. We next extend the longitudinal model to a two-stage model by using estimated parameters of the longitudinal process as covariates in a Cox proportional hazards model to assess prognostic factors of clinical failure including baseline characteristics, PSA trajectory, and HT.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Dataset of 2384 men included in three cohorts: University of Michigan, Ann Arbor, MI, USA (UM); Radiation Therapy Oncology Group (RTOG 9406); and William Beaumont Hospital, Detroit, MI, USA.
Key inclusion criteria (4 listed)
- clinically localized prostate cancer
- Clinical stage T1 to T4
- Node and metastasis negative
- Treated with external beam radiation therapy (RT).
Key exclusion criteria (1 listed)
- Patients with baseline or planned hormonotherapy
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 |
|---|---|---|
| external beam radiation therapy | Radiation | – |
Primary outcome
Number of Participants With Clinical Failure After Initiation of Radiotherapy
Time frame: within 10 years following initiation of radiotherapy
Clinical failure is defined as any of the following events following initiation of radiotherapy: distant metastases, nodal recurrence, or any palpable or biopsy-detected local recurrence three years after radiation; any local recurrence within three years of RT if the most previous PSA was>2 ng/ml; and death from prostate cancer.
1 secondary outcome
Number of Participants With Initiation of Salvage Therapy After Radiotherapy
Time frame: within 10 years following initiation of radiotherapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27587597Bellera C, Proust-Lima C, Joseph L, Richaud P, Taylor J, Sandler H, Hanley J, Mathoulin-Pelissier S. A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication. Stat Methods Med Res. 2018 Apr;27(4):1271-1281. doi: 10.1177/0962280216660127. Epub 2016 Sep 1.
- Individual participant dataSharing planned: Undecided
Related trials for Prostate Cancer
Active, not recruitingPhase 2/3
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer
Prostate Cancer, Oligometastasis
Not yet recruiting
Mind-Body Interventions for the Improvement of Quality of Life, Stress, and Sleep Quality Among Survivors of Breast, Prostate, Endometrial, or Colorectal Cancer
Breast Cancer Stage I, Colorectal Cancer
RecruitingPhase 3
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)
Prostate Cancer Metastatic
Active, not recruitingObservational study
Spatial Needle Placement Strategies and Pathological Concordance in Prostate Biopsy: A National Multicenter Retrospective Cohort Study
Prostate Cancer, Prostatic Neoplasms
Active, not recruitingPhase 2
177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With Prostate Cancer
Prostate Cancer
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.
Carine Bellera, PhD principal investigator
Institut Bergonié
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by Institut Bergonié 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 4 inclusion and 1 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 25 Jan 2021. 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?
Yes. Results are posted in the registry (first posted 21 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Clinical Failure After Initiation of Radiotherapy (time frame: within 10 years following initiation of radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03979079, which also lists 1 linked publication.
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 25 Jan 2021.