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

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ClinicalTrials.gov Identifier: NCT02269982
Recruitment Status : Active, not recruiting
First Posted : October 21, 2014
Last Update Posted : January 8, 2018
Sponsor:
Collaborators:
Weill Medical College of Cornell University
Johns Hopkins University
Dana-Farber Cancer Institute
Memorial Sloan Kettering Cancer Center
Epic Sciences
Prostate Cancer Foundation
Information provided by (Responsible Party):
Duke University

Brief 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.

Condition or disease Intervention/treatment
Prostate Cancer Device: AR-v7 assays

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
Actual Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Actual Study Start Date : April 2015
Estimated Primary Completion Date : November 30, 2018
Estimated Study Completion Date : November 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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



Primary Outcome Measures :
  1. Comparison of median progression free survival (PFS) to AR-v7 status [ Time Frame: 2 years ]

Secondary Outcome Measures :
  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: 2 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: 2 years ]
  3. Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC [ Time Frame: 2 years ]
  4. Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 2 years ]
  5. Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 2 years ]
  6. Change in neuroendocrine biomarkers during enzalutamide and taxane progression in men with mCRPC [ Time Frame: 2 years ]
  7. Associate high CTC heterogeneity with PFS, OS, and CTC genotype/phenotypes [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA
All 120 subjects will have blood collected at 3 time points for CTC-based AR-v7 analysis. Biopsy samples will be collected from up to 20 consenting subjects who are already undergoing a standard of care metastatic biopsy or from a research only biopsy.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   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).
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269982


Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Weill Medical College of Cornell University
Johns Hopkins University
Dana-Farber Cancer Institute
Memorial Sloan Kettering Cancer Center
Epic Sciences
Prostate Cancer Foundation
Investigators
Principal Investigator: Andrew J Armstrong, MD Duke University

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02269982     History of Changes
Other Study ID Numbers: Pro00056936
First Posted: October 21, 2014    Key Record Dates
Last Update Posted: January 8, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases