Clinical trial NCT02432001: Radiologically Guided Biopsies of mCRPC
Official title: Radiologically Guided Biopsies of Metastatic Castration Resistant Prostate Cancer (mCRPC) to Identify Adaptive Mechanisms of Resistance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostate Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: American Association for Cancer Research
First posted: 2015-05-01
Enrollment: 256
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Prostate Cancer

Brief summary: The purpose of this study is to better understand how cancer treatment may affect cancer cells. The research will involve genetic, molecular, cellular, and immunologic experiments using blood and tumor specimens. It is hoped that the information gained from these studies will lead to a greater understanding of castrate-resistant prostate cancer and potentially, improvements in cancer treatment.

This is a tissue collection protocol requiring image-guided biopsies of metastatic, castration-resistant prostate cancer (mCRPC). The investigators will focus on enrolling patients with metastatic CRPC who have progressed while receiving novel AR-targeted therapeutics such as abiraterone and enzalutamide. This population of patients was selected because resistance develops relatively rapidly following potent inhibitors of AR activity and the mechanisms of resistance have to be better understood. Without comprehensive analysis of mCRPC tumor, the investigators will never gain a full understanding of the biology driving resistance in human disease and developing rational co-targeting approaches will not be possible.


Eligibility criteria: Inclusion Criteria:

* History of histologically confirmed prostate cancer. Patients without histologically confirmed prostate cancer are eligible if both the treating physician and the study investigator agree that the patient's history is unambiguously indicative of advanced prostate cancer (e.g. high PSA responsive to Androgen Deprivation Therapy.)
* Radiographic evidence of metastatic disease amenable to image-guided biopsy of a metastatic site. Soft-tissue as well as bony metastatic lesions will be considered acceptable. Patients with locally advanced disease only (where the biopsy would be of a prostatic mass) are not eligible. Biopsy of newly emerging radiographic metastases is desired and preferable to the biopsy of previously existing lesions whenever possible.
* Platelets \>75,000/μl within 14 days prior to biopsy
* Prothrombin time (PT) or International Normalized Ratio (INR) and a partial thromboplastin time (PTT) \< 1.5 times the institutional upper limit of normal (ULN) within 14 days prior to biopsy.
* Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation for one week prior to the biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is agreement regarding the procedure between the treating physician, the interventional radiologist and the PI.
* Castrate levels of testosterone (testosterone \<50n g/dL) within 28 days prior to biopsy.
* Patients with significant congenital or acquired bleeding disorders (eg von Wildebrand's disease, acquired bleeding factor inhibitors) are not eligible.
* If no prior orchiectomy, medical castration therapy must continue while on study.
* Prostate-specific antigen (PSA) level obtained within 28 days prior to biopsy.
* Patients currently on first generation oral anti-androgens (flutamide, bicalutamide, nilutamide) must have progressed after at least 4 weeks of anti-androgen discontinuation.
* Patient's disease is currently progressing (in setting of testosterone \< 50 ng/dl), defined by any of the following criteria:
* PSA Progression: PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression for the purposes of eligibility.
* Soft tissue progression: by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Bone scan progression: the appearance of \>=2 new lesions. Symptomatic progression in an area of radiologically evident disease.
* One of the following criteria must be met:
* Evidence of disease progression (as defined above) following treatment with at least 2 months of abiraterone acetate, enzalutamide, or ARN509 - based therapy.
* Enrollment on a high priority clinical trial conducted by the West Coast Dream Team (WCDT). Examples include trials with biopsy obtained before abiraterone or enzalutamide therapy, and following development of resistance to those agent(s). This list is maintained by the lead site.
* Evidence of disease progression (as defined above) in patients with "aggressive phenotype" metastatic castration resistant prostate cancer (mCRPC) with at least one of the following clinical features
* Visceral or brain metastases
* Known small cell or neuro-endocrine subtypes (by Immunohistochemistry (IHC) or serum markers)
* Primary androgen deprivation therapy (ADT) resistance defined as a nadir PSA of \> 4 ng/dl after 7 months of primary androgen deprivation (with Testosterone \< 50 ng/dl.)
* Prior chemotherapy for Castration Resistant Prostate Cancer is not allowed
* Age \> 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance status 0-3
* Ability to understand and the willingness to sign a written informed consent document

Primary outcomes:
measure: Proportion of mCRPC patients with high androgen receptor activity
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Vancouver
country: Canada
facility: University of British Columbia
Study officials:
affiliation: University of California, San Francisco
name: Eric Small, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aggarwal R, Huang J, Alumkal JJ, Zhang L, Feng FY, Thomas GV, Weinstein AS, Friedl V, Zhang C, Witte ON, Lloyd P, Gleave M, Evans CP, Youngren J, Beer TM, Rettig M, Wong CK, True L, Foye A, Playdle D, Ryan CJ, Lara P, Chi KN, Uzunangelov V, Sokolov A, Newton Y, Beltran H, Demichelis F, Rubin MA, Stuart JM, Small EJ. Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. 2018 Aug 20;36(24):2492-2503. doi: 10.1200/JCO.2017.77.6880. Epub 2018 Jul 9.