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Prostate CancerPROPHECYNCT02269982

Prospective CiRculating prOstate Cancer Predictors in HighEr Risk mCRPC studY

An observational study of Prostate Cancer, run by Duke University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
AR-v7 assays
Type of treatment
Medical device
How many people
120 participants
Where
5 sitesUnited States
Study dates
14 May 2015to 30 Apr 2019
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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).
Show all 20Show fewer
  • 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
  • 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
  • PSA doubling time under 3 months on most recent therapy
  • Radiographic progression at entry based on new lesion(s) in bone, soft tissue, or visceral metastases
  • Age > 18 years.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

  • University of Chicago

    Chicago, Illinois, 60637

  • Duke University

    Durham, North Carolina, 27710

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Medical College of Cornell University

    New York, New York, 10065

Other trials in United States

About this study

Official title: 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.

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.

Conditions
Prostate Cancer
Being tested
AR-v7 assays
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AR-v7 assaysDevice

Study groups in NCT02269982
Study groupRoleWhat they receive
men with mCRPC prior to enzalutamide/abirateroneNot described
Receives: Device: AR-v7 assays

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 2 years

Secondary outcomes (7)

  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)

    Measured: 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)

    Measured: 4 years

  3. Determine molecular lesions in CTCs and ctDNA that consistently emerge during enzalutamide and taxane chemotherapy progression in men with mCRPC

    Measured: 4 years

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

    Measured: 4 years

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

    Measured: 4 years

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

    Measured: 4 years

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

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2014 (estimated)
  2. Study start14 May 2015
  3. Primary completion1 Sep 2017
  4. Study completion30 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02269982
Sponsor's protocol ID
Pro00056936
Acronym
PROPHECY
Status last verified
Jun 2019
First submitted
9 Oct 2014
Last updated
10 Jun 2019
Results posted
No
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

An observational study of Prostate Cancer, run by Duke University at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of median progression free survival (PFS) to AR-v7 status (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02269982, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019; AzTrials last refreshed its copy on 30 Oct 2026.

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