CTC Immune Checkpoint

Defining the Relevant Immune Checkpoints Expressed on Metastatic Prostate Cancer Circulating Tumor Cells

This pilot study will explore the prevalence of expression of four immune checkpoint biomarkers on circulating tumor cells (CTCs) from men with metastatic prostate cancer that are captured by EpCAM via the CellSearch method, and specifically defined as co expressing DAPI and cytokeratin, and lacking CD45 expression.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Device: CTC biomarker expression prevalence

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Duke Cancer Institute Patients

Description

Patients will be eligible for inclusion in this study only if all of the following criteria apply:

1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Small cell or neuroendocrine tumors of the prostate are also permitted.
2. Clinical or radiographic evidence of progressive metastatic disease, with progression defined as a rising PSA, new metastatic lesions (bone or soft tissue), or radiographic evidence of tumor growth on CT or MRI.
3. Age ≥ 18 years.
4. Ability to understand and the willingness to sign a written informed consent document.

In addition to meeting all of the above criteria, patients must meet all of the criteria for one of the following groups:

A) mCRPC starting sipuleucel-T (Provenge) with or without abiraterone acetate or enzalutamide

1. For patients with adenocarcinoma of the prostate (not applicable for patients with small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy): Castrate levels of testosterone (≤ 50 ng/dl)
2. Patient planning to start sipuleucel-T.
3. Enrollment prior to the initiation of sipuleucel-T.

B) mCRPC with visceral or high risk disease pre-abiraterone/enzalutamide

1. For patients with adenocarcinoma of the prostate (not applicable for patients with small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy): Castrate levels of testosterone (≤ 50 ng/dl)

2. Visceral OR high risk disease - must meet one of the following categories:

   • Visceral disease: Radiographic evidence of liver, adrenal, pulmonary, or brain metastases

   • High risk disease: Presence of at least 2 of the following factors:

     • Bone pain requiring opioids
     • Anemia (Hgb <13 g/dL)
     • Bone scan progression at baseline
     • >2 sites of metastatic disease
     • Karnofsky Performance Status (KPS) ≤ 70
     • PSA doubling time <3 months
3. Patient planning to start abiraterone acetate or enzalutamide.
4. Enrollment prior to the initiation of abiraterone acetate or enzalutamide.

C) Newly diagnosed metastatic castration sensitive prostate cancer (mCSPC) starting androgen deprivation therapy

1. Evidence of metastatic disease on radiographic imaging
2. Enrollment within 2 weeks of initiation of androgen deprivation therapy (ADT).
3. Lack of history of hypogonadism

D) Enzalutamide or abiraterone acetate resistant mCRPC

1. For patients with adenocarcinoma of the prostate (not applicable for patients with small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy): Castrate levels of testosterone (≤ 50 ng/dl)

2. Evidence of disease progression on or following enzalutamide or abiraterone acetate, as defined by one of the following:

   • Radiographic evidence of disease progression as defined by new bone scan lesions or growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator
   • Clinical progression of disease with cutaneous lesions or palpable lesions in absence of radiographic progression

Exclusion Criteria:

1. 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).
2. Treatment with an anthracycline (including mitoxantrone) within 1 week of CTC collection, as anthracyclines cause auto-fluorescence of cells.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; men with mCRPC starting sipuleucel-T (Provenge) with or without abiraterone acetate or enzalutamide will have CTC enumeration and immune checkpoint characterization at baseline, 3 months, 4-12 weeks after completion of sipuleucel-T, and at progression.	Device: CTC biomarker expression prevalence
Group B; men with mCRPC with visceral or high risk disease pre-abiraterone/enzalutamide will have CTC enumeration and immune checkpoint characterization at baseline, 3 months, and progression.	Device: CTC biomarker expression prevalence
Group C; men with high volume metastatic castration sensitive prostate cancer (mCSPC) starting hormonal therapy and docetaxel chemotherapy or who decline docetaxel chemotherapy will have CTC enumeration and immune checkpoint characterization at baseline, 3 months, and progression.	Device: CTC biomarker expression prevalence
Group D; men with enzalutamide or abiraterone acetate resistant mCRPC will have CTC enumeration and immune checkpoint characterization at baseline (i.e. progression on enzalutamide or abiraterone acetate) and 4-12 weeks after completion of next therapy (ex. radium-223 or chemotherapy)	Device: CTC biomarker expression prevalence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in expression of four immune checkpoint biomarkers (PD-L1, PD-L2, B7-H3, and CTLA-4) on circulating tumor cells (CTCs).	Baseline to 12 weeks
Change in expression of four immune checkpoint biomarkers (PD-L1, PD-L2, B7-H3, and CTLA-4) on circulating tumor cells (CTCs).	Baseline to 14 months (expected time of progression)

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): June 13, 2019
• Study Completion (Actual): June 13, 2019

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00063296

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No