Prospective CiRculating prOstate Cancer Predictors in HighEr Risk mCRPC studY (PROPHECY)

June 7, 2019 updated by: Duke University

Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)

This study will develop a first-in-man CTC-based molecular taxonomy of CRPC in the context of novel AR-directed therapies, categorize different patterns of resistance in this disease setting, and describe their evolution over time and treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will construct a multi-center clinical database of men before and after treatment with abiraterone acetate, enzalutamide, and taxane chemotherapy, and will comprehensively analyze CTC DNA for copy gains/losses and whole exome sequencing for acquired mutations, CTC RNA for AR-variants and evidence of epithelial plasticity, and plasma circulating tumor DNA (ctDNA) for whole exome sequencing. Significantly, the investigators will pair the presence of key proposed circulating biomarkers of treatment resistance with patient outcomes on these systemic therapies for the purpose of developing predictive biomarkers that may have direct clinical utility in guiding choice of therapies. It is proposed that specific AR-v's (i.e. AR-v7), biomarkers of epithelial plasticity, and microtubule interacting protein variants will convey docetaxel resistance and be enriched in men failing abiraterone acetate or enzalutamide, while other AR genomic events (AR amplification, AR-v567es, AR mutations, GR overexpression) will be responsive to taxane chemotherapy. This work represents a first-in-field comprehensive analysis of CTC molecular profiles for the development of a CTC molecular taxonomy of mCRPC.

Study Type

Observational

Enrollment (Actual)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10065
        • Weill Medical College of Cornell University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

The study population includes men with progressive metastatic castration resistant prostate cancer (mCRPC).

Description

Inclusion Criteria:

  1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Pure small cell or neuroendocrine tumors of the prostate are not permitted.
  2. Clinical or radiographic evidence of metastatic disease.
  3. Planned therapy with either enzalutamide and/or abiraterone acetate within the coming 6 weeks
  4. Castrate levels of testosterone (<50 ng/dl) at most recent assessment and/or documented ongoing Androgen Deprivation Therapy for at lease three months.

  5. Evidence of disease progression on or following most recent therapy as evidenced by at least one of the following:

    • Radiographic evidence of disease progression as defined by one or more new bone scan lesions that is not consistent with flare/healing, or growth of soft tissue/visceral metastases to greater than one centimeter (cm) in longest diameter (2 cm shortest diameter for lymph nodes).
    • Clinical progression as defined by the treating physician (such as pain progression)
    • Consecutive PSA rises meeting PSA progression criteria as determined by PCWG2 criteria (increase that is >25% and >2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later)

  6. At least two of the following high risk features during screening for rapid disease progression:

    1. Anemia with a hemoglobin <12.0 g/dl
    2. Elevated alkaline phosphatase above the institution upper limit of normal
    3. High lactate dehydrogenase (LDH) above the upper limit of normal
    4. Prior therapy with enzalutamide, abiraterone acetate, or orteronel. Patients are not permitted if they are continuing on the same therapy or restarting a therapy that they have been exposed to in the past.
    5. Presence of visceral metastasis on imaging
    6. Presence of clinically significant pain requiring opioid analgesia
    7. Patients with a Cellsearch CTC > 5 cells per 7.5 mL whole blood (if available as standard of care) are eligible without additional high risk features
    8. PSA doubling time under 3 months on most recent therapy
    9. Radiographic progression at entry based on new lesion(s) in bone, soft tissue, or visceral metastases
  7. Age > 18 years.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. History of intercurrent or past medical or psychiatric illness that would make participation in a blood drawing protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s).
  2. Treatment with an anthracycline or mitoxantrone within 1 week of CTC collection
  3. Prior docetaxel in the castration resistant metastatic setting. Patients treated with docetaxel for metastatic castration sensitive disease will be eligible.
  4. Unwillingness to be followed longitudinally for serial CTC biomarker studies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
men with mCRPC prior to enzalutamide/abiraterone
Device: AR-v7 assays

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Comparison of median progression free survival (PFS) to AR-v7 status
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine the prevalence of defined categories of a molecular taxonomy of mCRPC using CTC biomarkers and correlate each to clinical benefit (PSA response, PFS)
Time Frame: 4 years
4 years
Compare levels of circulating epithelial to mesenchymal transition (EMT) and other epithelial plasticity (EP) biomarkers with mCRPC taxonomic categories and clinical outcomes (PSA decline rates, PFS)
Time Frame: 4 years
4 years
Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC
Time Frame: 4 years
4 years
Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS)
Time Frame: 4 years
4 years
Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS)
Time Frame: 4 years
4 years
Change in neuroendocrine biomarkers during enzalutamide and taxane progression in men with mCRPC
Time Frame: 4 years
4 years
Associate high CTC heterogeneity with PFS, OS, and CTC genotype/phenotypes
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Johns Hopkins University
Memorial Sloan Kettering Cancer Center
Dana-Farber Cancer Institute
Weill Medical College of Cornell University
Prostate Cancer Foundation
Epic Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2015

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

April 30, 2019

Study Registration Dates

First Submitted

October 9, 2014

First Submitted That Met QC Criteria

October 17, 2014

First Posted (Estimate)

October 21, 2014

Study Record Updates

Last Update Posted (Actual)

June 10, 2019

Last Update Submitted That Met QC Criteria

June 7, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00056936

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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