Summary

for males ages 18 years and up (full criteria)
at San Francisco, California
study started
estimated completion
Rahul Aggarwal

Description

Summary

This is a tissue and blood collection protocol requiring image-guided biopsies of metastatic prostate cancer. Whenever possible, a new bone lesion or new/progressing soft tissue lesion will be chosen for biopsy as opposed to radiographically stable lesion. Patients will be enrolled in parallel into one of six possible cohorts based upon planned modality of systemic therapy following baseline tumor biopsy and/or disease features at time of study entry: (A) Androgen signaling inhibition, (B) Immunotherapy, (C) Radiotherapy, (D) Targeted Therapy/Investigational therapeutic, (E) DNA damage response pathway, or (F) Aggressive variant disease.

Official Title

Precision Oncology and Molecular Targeting in Advanced Prostate Cancer: Identifying Predictive Markers of Response (The "PROMOTE" Study)

Details

After performing tumor biopsies and blood collection and processing the biopsies and research blood for comprehensive molecular analysis using established methods for RNA and DNA analysis, we will use Pathway Recognition using Data Integration on Genomic Models (PARADIGM) and Differential Pathway Signature Correlation (DiPSC), computational approaches to pathway activity and predictive signature identification developed at University of California, Santa Cruz. We will also collect blood samples (for circulating tumor DNA, plasma, and serum) and circulating tumor cells from participating patients. Residual paraffin- embedded blocks, frozen tissue, and blood products (serum, plasma, and circulating cells) will be stored in a repository for future testing of candidate predictive markers identified during microarray analysis. We will utilize only Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories(e.g. Strata Oncology) to identify genetic mutations within mCRPC tumors to provide genetic information that can be returned to patient to potentially inform treatment decisions.

Certain genomic sequencing will be performed by Strata Oncology.

Following biopsy and baseline peripheral blood collection, patients will be treated per investigator discretion, with treatment corresponding to assigned patient cohort and initiated within 42 days following baseline tumor biopsy and/or research blood collection. Patients will be evaluated for response to therapy with monthly serum prostate-specific antigen (PSA) measurements (may be done at UCSF or at local laboratory) along with restaging scans (bone scan + CT abd/pelvis) (UCSF or local radiology facility). Outcomes on treatment post-biopsy will be recorded, including maximal PSA decline, date of radiographic progression.

At the time of disease progression by Prostate Cancer Working Group 2 (PCWG2) criteria, patients may undergo optional repeat assessment for metastatic tumor biopsy, along with mandatory blood collection for analysis of circulating tumor DNA and circulating tumor cells (CTCs). Following second biopsy at progression, patients should continue to be followed for response to subsequent therapy.

All patients will be followed for long term survival with every 3 month telephone calls and/or chart review.

Keywords

Prostate Cancer Castration Resistant Metastatic Prostatic Neoplasms Androgens Systemic therapy

Eligibility

For males ages 18 years and up

Inclusion Criteria:

  • History of histologically confirmed prostate cancer. Patients without histologically confirmed prostate cancer are eligible if both the treating physician and the study PI 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 or excisional 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 or progressive metastases is desired and preferable to the biopsy of previously existing stable lesions whenever possible. Patients without lesion amenable to biopsy are still eligible, and have the option of re-assessment for potential of metastatic tumor biopsy upon progression as outlined in the study calendar.
  • For patients with metastatic lesion amenable for biopsy:
  • Platelets > = 75,000/microliter (μl)
  • Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) < = 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 prior to the biopsy as per usual standard of care. 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.
  • Patients with significant congenital or acquired bleeding disorders (eg type 3 von Wildebrand's disease, acquired bleeding factor inhibitors) are not eligible.
  • Age > 18 yrs
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  • Ability to understand and the willingness to sign a written informed consent.
  • Metastatic, castration resistant disease by Prostate Cancer Working Group 2 (PCWG2) criteria, with progression on most recently applied systemic therapy prior to study registration, as defined by:
  • PSA Progression: PSA level of at least 2 nanograms (ng)/milliliter (ml) which has risen on at least 2 successive occasions, at least one week apart and/or
  • Soft tissue progression: by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or
  • Bone scan progression: the appearance of ≥ 2 new lesions and/or
  • Symptomatic progression in an area of radiologically evident disease
  • Documented serum testosterone < 50 ng/deciliter (dL). Patients without prior bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue for duration of study. Patients with previously documented de novo primary small cell carcinoma of the prostate are exempt from this criterion. If serum for analysis of testosterone level has been collected but result not available by day of scheduled baseline biopsy, patient may still be eligible for study participation upon at the discretion of the Principal Investigator.
  • Patients must possess one of the following criteria:
  • Planned treatment within 42 days following baseline tumor biopsy and/or research blood collection with androgen signaling inhibitor excluding enzalutamide (cohort A), immunotherapy (cohort B), radiotherapy (cohort C), investigational therapeutic (cohort D), or agent targeting the DNA repair pathway including but not limited to platinum chemotherapy or poly adenosine diphosphate-ribose polymerase (PARP) inhibition (cohort E). Therapeutic combinations are allowed and as treatment may fall into more than one category, cohort assignment will be per PI discretion.
  • Aggressive variant cancer (cohort F), defined by one or more of the following:
  • Presence of one or more visceral organ metastases
  • Serum neuron specific enolase and/or chromogranin A >ULN
  • Progression by PCWG2 criteria within 12 months following initiation of primary androgen deprivation therapy (ADT) +/- chemotherapy for metastatic hormone sensitive prostate cancer
  • Prior histologic evidence of small cell and/or intermediate atypical carcinoma differentiation

Location

  • University of California, San Francisco accepting new patients
    San Francisco California 94158 United States

Lead Scientist

  • Rahul Aggarwal
    I am a Medical Oncologist within the Division of Hematology/Oncology at the University of California San Francisco. My clinical practice focuses on patients with advanced solid tumor malignancies with a particular emphasis on genitourinary malignancies including prostate, kidney, bladder, and testicular cancer. I serve as the Co-Leader for the GU Medical Oncology program at UCSF.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02735252
Study Type
Interventional
Last Updated