CTC Immune Checkpoint

• ClinicalTrials.gov Identifier: NCT02456571
• Recruitment Status: Completed
• First Posted: May 28, 2015
• Last Update Posted: July 9, 2019
• Sponsor: Duke University
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Prostate Cancer	Device: CTC biomarker expression prevalence

Study Design

• Study Type: Observational
• Actual Enrollment: 38 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Defining the Relevant Immune Checkpoints Expressed on Metastatic Prostate Cancer Circulating Tumor Cells
• Actual Study Start Date: November 2016
• Actual Primary Completion Date: June 13, 2019
• Actual Study Completion Date: June 13, 2019

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Duke Cancer Institute Patients

Criteria

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.

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Janssen Research & Development, LLC

Investigators

• Principal Investigator: Andrew J Armstrong, MD; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02456571
• Other Study ID Numbers: Pro00063296
• First Posted: May 28, 2015
• Last Update Posted: July 9, 2019
• Last Verified: July 2019

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases