Radiologically Guided Biopsies of mCRPC

Sponsor
University of California, San Francisco (Other)
Overall Status
Completed
CT.gov ID
NCT02432001
Collaborator
American Association for Cancer Research (Other)
256
Enrollment
5
Locations
82.3
Actual Duration (Months)
51.2
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Procedure: Image-Guided Biopsies

Study Design

Study Type:
Observational
Actual Enrollment :
256 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Radiologically Guided Biopsies of Metastatic Castration Resistant Prostate Cancer (mCRPC) to Identify Adaptive Mechanisms of Resistance
Actual Study Start Date :
Feb 22, 2013
Actual Primary Completion Date :
Jan 1, 2020
Actual Study Completion Date :
Jan 1, 2020

Arms and Interventions

ArmIntervention/Treatment
Image-Guided Biopsies

Image-guided biopsies will be performed at the Dream Team Site enrolling the patient. Lesions will be chosen based upon the strength of the evidence suggesting the presence of metastasis and with the goal of minimizing patient risk. Soft tissue lesions and lesions with documented radiologic progression should be prioritized for biopsy. If the Radiologist in charge of the procedure cannot identify a lesion amenable for biopsy, the patient will be considered a screening failure.

Procedure: Image-Guided Biopsies

Outcome Measures

Primary Outcome Measures

  1. Proportion of mCRPC patients with high androgen receptor activity [Up to 2 years]

    Determined by a gene-expression-based signature for Androgen Receptor activity having a probability of >0.50

Secondary Outcome Measures

  1. Progression Free Survival [Up to 2 years]

    Measured from the start of therapy after the baseline biopsy until progression. Patients not progressing will be censored at the date of last clinical follow-up or date of last contact, respectively.

  2. Overall Survival [Up to 2 years]

    Measured from the start of therapy after the baseline biopsy until death. Patients not progressing or dying will be censored at the date of last clinical follow-up or date of last contact, respectively

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of California, DavisDavisCaliforniaUnited States95616
2University of California, Los AngelesLos AngelesCaliforniaUnited States90095
3University of CaliforniaSan FranciscoCaliforniaUnited States94143
4Oregon Health & Science UniversityPortlandOregonUnited States97239
5University of British ColumbiaVancouverCanada

Sponsors and Collaborators

  • University of California, San Francisco
  • American Association for Cancer Research

Investigators

  • Principal Investigator: Eric Small, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02432001
Other Study ID Numbers:
  • 125519
First Posted:
May 1, 2015
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021