Prospective CiRculating prOstate Cancer Predictors in HighEr Risk mCRPC studY
PROPHECY
Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)
1 other identifier
observational
120
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started May 2015
Longer than P75 for all trials
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2014
CompletedFirst Posted
Study publicly available on registry
October 21, 2014
CompletedStudy Start
First participant enrolled
May 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2019
CompletedJune 10, 2019
June 1, 2019
2.3 years
October 9, 2014
June 7, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Comparison of median progression free survival (PFS) to AR-v7 status
2 years
Secondary Outcomes (7)
Determine the prevalence of defined categories of a molecular taxonomy of mCRPC using CTC biomarkers and correlate each to clinical benefit (PSA response, PFS)
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)
4 years
Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC
4 years
Correlate specific AR-v7 assays with clinical outcomes (PSA decline rates, PFS)
4 years
Correlatate other AR-variants with clinical outcomes (PSA decline rates, PFS)
4 years
- +2 more secondary outcomes
Study Arms (1)
men with mCRPC prior to enzalutamide/abiraterone
Interventions
Eligibility Criteria
The study population includes men with progressive metastatic castration resistant prostate cancer (mCRPC).
You may qualify if:
- Histologically confirmed diagnosis of adenocarcinoma of the prostate. Pure small cell or neuroendocrine tumors of the prostate are not permitted.
- Clinical or radiographic evidence of metastatic disease.
- Planned therapy with either enzalutamide and/or abiraterone acetate within the coming 6 weeks
- Castrate levels of testosterone (\<50 ng/dl) at most recent assessment and/or documented ongoing Androgen Deprivation Therapy for at lease three months.
- 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)
- At least two of the following high risk features during screening for rapid disease progression:
- Anemia with a hemoglobin \<12.0 g/dl
- Elevated alkaline phosphatase above the institution upper limit of normal
- High lactate dehydrogenase (LDH) above the upper limit of normal
- 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.
- Presence of visceral metastasis on imaging
- Presence of clinically significant pain requiring opioid analgesia
- +5 more criteria
You may not qualify if:
- 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).
- Treatment with an anthracycline or mitoxantrone within 1 week of CTC collection
- Prior docetaxel in the castration resistant metastatic setting. Patients treated with docetaxel for metastatic castration sensitive disease will be eligible.
- Unwillingness to be followed longitudinally for serial CTC biomarker studies.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Duke Universitylead
- Weill Medical College of Cornell Universitycollaborator
- Johns Hopkins Universitycollaborator
- Dana-Farber Cancer Institutecollaborator
- Memorial Sloan Kettering Cancer Centercollaborator
- Epic Sciencescollaborator
- Prostate Cancer Foundationcollaborator
Study Sites (5)
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
Related Publications (3)
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.
PMID: 33894633DERIVEDGupta 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.
PMID: 33771885DERIVEDArmstrong 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.
PMID: 30865549DERIVED
Biospecimen
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.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew J Armstrong, MD
Duke University
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 9, 2014
First Posted
October 21, 2014
Study Start
May 14, 2015
Primary Completion
September 1, 2017
Study Completion
April 30, 2019
Last Updated
June 10, 2019
Record last verified: 2019-06