PROMOTE: Identifying Predictive Markers of Response for Genitourinary Cancer

NCT02735252 | Active Not Recruiting FDA Device

• 2 other identifiers: 155518NCI-2018-02052
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

This is a tissue and blood collection protocol requiring image-guided biopsies of metastatic prostate cancer and other genitourinary malignancies including renal cell carcinoma and urothelial carcinoma. 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 into one of several parallel cohorts based upon disease status or type and the planned systemic therapy following baseline tumor biopsy: (A) Androgen signaling inhibition, (B) Immunotherapy, (C) Radiotherapy, (D) Targeted Therapy/Investigational therapeutic, (E) DNA damage response pathway, (F) Aggressive variant disease, (G1) Castration-sensitive ADT naïve and ADT \< 3 months), or (G2) Castration-sensitive pre-treated with sub-optimal PSA nadir \>0.2 ng/ml, (R) metastatic renal cell carcinoma and metastatic and (U) urothelial carcinoma.

Conditions

Prostate Cancer; Advanced Renal Cell Carcinoma; Advanced Urothelial Carcinoma; Genitourinary Cancer

Keywords

Castration Resistant; Metastatic

Outcome Measures

Primary Outcomes (4)

• Correlation of Treatment Benefit by group

  Using PARADIGM and DiPSC tools, the investigators will discover genetic expression and clinical factors that are predictive of treatment benefit within each treatment cohort using correlative analysis.

  Up to 5 years

• Positive Predictive Value (PPV)

  Supervised analysis using response / benefit from the experimental therapy to assess feasibility of pattern recognition/discovery of factors that are associated with response and generate a positive predictive value. Positive predictive value is the probability that participants with a positive test truly have the disease. Positive Predictive Value: True Positive / (True Positive +False Positive)

  Up to 5 years

• Median Progression-Free Survival (PFS)

  PFS is measured from the time in months of the initiation of therapy after biopsy at enrollment until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death. For participants initiating treatment, their screening clinical, laboratory, and radiological status will be used as a baseline. Progression is a composite endpoint that can be based upon prostate specific antigen (PSA), objective measures of disease (Response Evaluation Criteria in Solid Tumors (RECIST v.1.1), symptoms, or death.

  Up to 5 years

• Median Overall Survival (OS)

  OS is measured from the time in months of the initiation of therapy after biopsy at enrollment until death.

  Up to 5 years

Secondary Outcomes (4)

• Prostate-specific antigen (PSA) Response Rate

  Up to 5 years

• Objective Response Rate (ORR)

  Up to 5 years

• Number of participants with presence of somatic mutations

  Up to 5 years

• Comparison of pathway activity signatures and overall survival

  Up to 5 years

Study Arms (10)

Group A: Androgen Signaling Inhibition

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving treatments that inhibit androgen signaling to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group B: Immunotherapy

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving immunotherapy to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group C: Radiotherapy

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving radiotherapy to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group D: Targeted Therapy Not Otherwise Specified

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving targeted therapy and investigational therapeutics to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group E: DNA Damage Response

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving therapies that target DNA damage response pathways to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group F: Aggressive Variant Disease

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients with variants of disease that display aggressive behavior to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group G1: Castration Sensitive, ADT naïve and ADT < 3 months

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving therapies that target DNA damage response pathways to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group G2:Castration Sensitive,Pre-treated w/ sub-optimal PSA

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving therapies that target DNA damage response pathways to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Group R: Advanced Renal Cell Carcinoma

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving therapies that target DNA damage response pathways to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Cohort U: Advanced Urothelial Carcinoma

EXPERIMENTAL

Tumor biopsies: required prior to treatment and optional at time of disease progression. Blood draws: required prior to treatment, every 3 months during treatment, and at time of disease progression. Molecular markers will be studied in patients receiving therapies that target DNA damage response pathways to identify predictors of benefit and/or response. Treatments are assigned per investigator discretion.

Other: Systemic therapy; Device: StrataNGS

Interventions

Systemic therapy OTHER

Systemic therapy is selected by the physician and is not restricted by the study. Molecular testing will be performed on tissue and blood to identify patterns and relationships with clinical outcomes in each group.

Cohort U: Advanced Urothelial Carcinoma; Group A: Androgen Signaling Inhibition; Group B: Immunotherapy; Group C: Radiotherapy; Group D: Targeted Therapy Not Otherwise Specified; Group E: DNA Damage Response; Group F: Aggressive Variant Disease; Group G1: Castration Sensitive, ADT naïve and ADT < 3 months; Group G2:Castration Sensitive,Pre-treated w/ sub-optimal PSA; Group R: Advanced Renal Cell Carcinoma

StrataNGS DEVICE

CLIA-approved assay that is being performed as part of standard of care genomic profiling of patients tumor biopsies. The product currently covers about 90 cancer genes and is able to pick up all the known mutations and other types of genetic alterations across them, he added

Cohort U: Advanced Urothelial Carcinoma; Group A: Androgen Signaling Inhibition; Group B: Immunotherapy; Group C: Radiotherapy; Group D: Targeted Therapy Not Otherwise Specified; Group E: DNA Damage Response; Group F: Aggressive Variant Disease; Group G1: Castration Sensitive, ADT naïve and ADT < 3 months; Group G2:Castration Sensitive,Pre-treated w/ sub-optimal PSA; Group R: Advanced Renal Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of histologically confirmed prostate cancer, or other advanced / metastatic genitourinary malignancies for cohorts R (renal cell carcinoma) and U (urothelial carcinoma). Participants without histologically confirmed 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 Prostate-specific antigen (PSA) responsive to Androgen Deprivation Therapy in prostate cancer)
• 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. Participants 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 participants 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.
• Participants with significant congenital or acquired bleeding disorders (e.g 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.
• Progression on or following most recent systemic therapy given for:
• Metastatic Renal Cell Carcinoma (RCC) or metastatic urothelial carcinoma (UC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or for metastatic castration resistant prostate cancer (mCRPC) by Prostate Cancer Working Group 2 (PCWG2) criteria, with progression as defined by one or more of the following:
• PSA Progression: PSA level of at least 2 nanograms (ng)/milliliter (ml) which has risen on at least 2 separate measurements, at least one week apart (for prostate cancer participants only)
• Disease progression by RECIST v1.1
• Bone scan progression: the appearance of \>= 2 new lesions (for prostate cancer participants only)

Sponsors & Collaborators

• University of California, San Francisco: lead
• Prostate Cancer Foundation: collaborator
• Strata Oncology: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Urogenital Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: April 12, 2016
• Study Start: May 25, 2016
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)