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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 : February 1, 2019
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

Tracking Information
First Submitted Date October 9, 2014
First Posted Date October 21, 2014
Last Update Posted Date February 1, 2019
Actual Study Start Date May 14, 2015
Actual Primary Completion Date September 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 6, 2017)
Comparison of median progression free survival (PFS) to AR-v7 status [ Time Frame: 2 years ]
Original Primary Outcome Measures
 (submitted: October 17, 2014)
Comparison of median progression free survival (PFS) and overall survival (OS) to AR-v7 status [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT02269982 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 30, 2019)
  • 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 ]
  • 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 ]
  • Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC [ Time Frame: 4 years ]
  • Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 4 years ]
  • Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 4 years ]
  • Change in neuroendocrine biomarkers during enzalutamide and taxane progression in men with mCRPC [ Time Frame: 4 years ]
  • Associate high CTC heterogeneity with PFS, OS, and CTC genotype/phenotypes [ Time Frame: 4 years ]
Original Secondary Outcome Measures
 (submitted: October 17, 2014)
  • 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 ]
  • 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 ]
  • Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC [ Time Frame: 2 years ]
  • Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 2 years ]
  • Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS) [ Time Frame: 2 years ]
  • Change in neuroendocrine biomarkers during enzalutamide and taxane progression in men with mCRPC [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Prospective CiRculating prOstate Cancer Predictors in HighEr Risk mCRPC studY
Official Title Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
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.
Sampling Method Non-Probability Sample
Study Population The study population includes men with progressive metastatic castration resistant prostate cancer (mCRPC).
Condition Prostate Cancer
Intervention Device: AR-v7 assays
Study Groups/Cohorts men with mCRPC prior to enzalutamide/abiraterone
Intervention: Device: AR-v7 assays
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: October 17, 2014)
120
Original Estimated Enrollment Same as current
Estimated Study Completion Date April 30, 2019
Actual Primary Completion Date September 1, 2017   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02269982
Other Study ID Numbers Pro00056936
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Duke University
Study 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
Investigators
Principal Investigator: Andrew J Armstrong, MD Duke University
PRS Account Duke University
Verification Date January 2019