Clinical trial NCT03017794: Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy
Official title: Evaluation of Neuroendocrine Differentiation as a Potential Mechanism of Tumor Recurrence Following Radiotherapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Prostate Cancer
Keywords: Radiotherapy
Chromogranin A
Neuroendocrine differentiation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2017-01-11
Enrollment: 118
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Post-RT CgA and Gleason Score (GS)
timeFrame: 5 years 6 months
measure: Chromogranin A (CgA) levels
timeFrame: 5 years 6 months
Secondary outcomes:
measure: Androgen deprivation therapy (ADT) and CgA
timeFrame: 5 years 6 months
measure: Post--therapy CgA in photon-based RT and proton-based RT
timeFrame: 5 years 6 months
measure: CgA and biochemical recurrence
timeFrame: 5 years 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ryan M. Phillips, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: