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CompletedNCT02269982PROPHECYUpdated Jun 10, 2019

Prospective CiRculating prOstate Cancer Predictors in HighEr Risk mCRPC studY

An observational study in Prostate Cancer, sponsored by Duke University. Completed at 5 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-06-10.

Sponsored by Duke University · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
120
Ages
18 Years and older
Sex
Male
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Study summary

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.

Read the 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.

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Conditions studied

  • Prostate Cancer

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In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 120 is below the median of 200 across 1,181 observational studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.

Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

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

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

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.
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
120 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • men with mCRPC prior to enzalutamide/abiraterone

    Device: AR-v7 assays

Interventions

  • DeviceAR-v7 assays
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What researchers measure

Primary outcomes

  1. Comparison of median progression free survival (PFS) to AR-v7 status

    Time frame: 2 years

Secondary outcomes

  1. 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

  2. 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

  3. 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. Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS)

    Time frame: 4 years

  5. Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS)

    Time frame: 4 years

  6. Change in neuroendocrine biomarkers during enzalutamide and taxane progression in men with mCRPC

    Time frame: 4 years

  7. Associate high CTC heterogeneity with PFS, OS, and CTC genotype/phenotypes

    Time frame: 4 years

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Study locations

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

Publications

  • Scher HI, Armstrong AJ, Schonhoft JD, Gill A, Zhao JL, Barnett E, Carbone E, Lu J, Antonarakis ES, Luo J, Tagawa S, Dos Anjos CH, Yang Q, George D, Szmulewitz R, Danila DC, Wenstrup R, Gonen M, Halabi S. Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer. Eur J Cancer. 2021 Jun;150:83-94. doi: 10.1016/j.ejca.2021.02.042. Epub 2021 Apr 21. PubMed 33894633 ↗
  • Gupta S, Halabi S, Kemeny G, Anand M, Giannakakou P, Nanus DM, George DJ, Gregory SG, Armstrong AJ. Circulating Tumor Cell Genomic Evolution and Hormone Therapy Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer. Mol Cancer Res. 2021 Jun;19(6):1040-1050. doi: 10.1158/1541-7786.MCR-20-0975. Epub 2021 Mar 26. PubMed 33771885 ↗
  • Armstrong AJ, Halabi S, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ, Danila DC, Healy P, Anand M, Rothwell CJ, Rasmussen J, Thornburg B, Berry WR, Wilder RS, Lu C, Chen Y, Silberstein JL, Kemeny G, Galletti G, Somarelli JA, Gupta S, Gregory SG, Scher HI, Dittamore R, Tagawa ST, Antonarakis ES, George DJ. Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study. J Clin Oncol. 2019 May 1;37(13):1120-1129. doi: 10.1200/JCO.18.01731. Epub 2019 Mar 13. PubMed 30865549 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 10, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02269982
Lead sponsor
Duke University
Collaborators
Weill Medical College of Cornell University, Johns Hopkins University, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Epic Sciences, Prostate Cancer Foundation
Responsible party
Sponsor
First posted
Oct 21, 2014
Start date
May 14, 2015
Primary completion
Sep 1, 2017
Completion
Apr 30, 2019
Last update
Jun 10, 2019

Study contacts

Andrew J Armstrong, MD
principal investigator · Duke University

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2019. You cannot join it, but the record below documents what was studied.

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