Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy

This is a pilot study to test a hypothesis that a greater increase in serum chromogranin A (CgA) after a definitive radiotherapy (RT) with or without androgen deprivation therapy (ADT) is associated with a higher risk of prostate cancer recurrence after RT. Serum CgA level is measured before the start of RT and/or the start of neoadjuvant ADT for patients undergoing a definitive RT with or without ADT. CgA is also measured at various pre-defined post-RT time points. The study will analyze the followings: 1. Change in CgA level at various pre-defined post-RT time points from the baseline, 2. Correlation between the extent of post-therapy CgA change and Gleason score of malignancy, 3. Correlation between the extent of post-therapy CgA change and treatment outcome.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer

Detailed Description

Neuroendocrine differentiation (NED) in prostate cancer is a well-recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like) cells. Accumulated evidences have suggested that the prevalence of NE-like cells is associated with disease progression and poor prognosis.

NED can be induced by a therapeutic agent. Such therapeutic agents include RT and ADT. RT-induced NED represents a novel pathway by which prostate cancer cells survive radiotherapy and contribute to treatment failure and tumor recurrence. Chromogranin A is the serum biomarker for NED and correlates well with CgA-positive staining in biopsy specimens. It has been reported that elevated serum CgA is associated with poor therapeutic response, androgen-independent growth, and biochemical recurrence.

The study tests whether the extent of serum CgA increase by RT +/- ADT, which reflects radiation-induced NED, is correlated with the risk of prostate cancer recurrence following RT and a Gleason score of prostate carcinoma.

• Study Type: Observational
• Enrollment (Actual): 118

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients that are to receive either definitive RT +/- ADT as a primary therapy or salvage RT +/- ADT as a salvage therapy for a biochemical relapse with local recurrence in the prostatic fossa following a radical prostatectomy.

Description

Inclusion Criteria:

• Clinically localized prostate carcinoma, T1-T4 N0M0, any Gleason Score, any prostate-specific antigen (PSA), or Biochemical relapse with clinically suspicious (based on MRI or clinical examination) or biopsy-proven local recurrence in the prostatic fossa after a radical prostatectomy
• ≥18 years old
• Histologic diagnosis of prostate adenocarcinoma
• Signed informed consent

Exclusion Criteria:

• Biochemical relapse alone without clinically suspicious (i.e. no suspicious lesion on MRI of the prostatic bed) or biopsy-proven local recurrence in the prostatic fossa
• Regional pelvic node metastasis (N1)
• Distant metastasis (M1)
• Concurrent or previous cytotoxic medications
• Medical or psychological conditions that in the opinion of the investigator would not allow follow-up

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Gleason score 6 or less; Prostate adenocarcinoma with Gleason score 6 or less
Gleason score 7; Prostate adenocarcinoma with Gleason score 7
Gleason score 8 -10; Prostate adenocarcinoma with Gleason score 8 -10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlate the extent of post-RT CgA change with Gleason score of malignancy	18 months
Correlate the extent of post-RT CgA change with treatment outcome, using biochemical recurrence as an endpoint	60 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Examine the extent of CgA change at various post-RT time points	18 months
Examine the effect of ADT on CgA level for patients receiving RT + ADT, and Compare the extent of post-therapy CgA change between patients receiving RT alone and those undergoing RT + ADT	18 months
Compare the extent of post-therapy CgA change between patients receiving photon-based RT and those undergoing proton-based RT	24 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: C. Richard Choo, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2017
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimated): January 11, 2017

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Chromogranin A; Neuroendocrine differentiation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: 16-008637; NCI-2023-00596 (Registry Identifier: CTRP (Clinical Trials Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No