Clinical trial NCT04243473: Biopsy Collection for Men Undergoing Brachytherapy for Prostate Cancer
Official title: Prostate Tissue Biopsy Collection for Men Undergoing Brachytherapy for Treatment of Localized or Locally Advanced Prostate Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Prostate Cancer
Keywords: Brachytherapy
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2020-01-28
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population will be patients for whom the treatment plan includes brachytherapy for localized or locally advanced adenocarcinoma of the prostate who are seen in consultation at the Department of Radiation Oncology and Molecular Radiation Sciences.

Brief summary: The primary goal of this tissue collection protocol is to establish a framework for the acquisition and banking of biospecimen collected from men undergoing brachytherapy. Biopsies of the prostate is an invasive procedure; however, in this tissue collection protocol, biopsies are acquired intraoperatively while patients are prepped for brachytherapy seed placement, thus minimizing the inconvenience of the biopsy procedure for patients. The utility of these biopsies will provide a valuable resource for molecular assessments.

Detailed description: Many patients with metastatic prostate cancer who succumb to the disease are initially diagnosed with localized prostate cancer, where treatment has the potential to be curative. For men initially diagnosed with high risk or locally advanced prostate cancer, nearly 50% develop recurrence after primary therapy and can eventually progress to life-threatening metastatic disease. Combined androgen deprivation therapy (ADT) with ionizing radiation (IR) is the current mainstay of therapy for such men with high-risk prostate cancer. While it is likely that undetected, microscopic disseminated disease leads to the inability to cure in some men, there is also emerging evidence that escalating local therapy may still have benefit. It has been reported that metastasis-free survival and overall survival were significantly improved in men with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) with brachytherapy boost compared to men treated with EBRT alone, or with radical prostatectomy. The observation that enhanced IR-based local therapy could improve outcomes supports the notion that it is not microscopic systemic disease alone that leads to treatment failures of high-risk prostate cancer, but that more aggressive local management could still play a significant role.

A key question in the management of high risk prostate cancer is how can the investigators predict whether a patient with local or metastatic prostate cancer will have complete response with current IR-based therapy paradigms, or if patients would benefit from more aggressive dosing regimens despite a potential for increased adverse effects. A major limitation to developing effective strategies for predicting treatment response to conventional vs. more aggressive dosing regiments has been a paucity of tissues from patients undergoing radiation therapy, including at baseline and during follow up, as well as a lack of the molecular, cell biological, and biochemical states of the cancer and microenvironmental cells in such tissues. The availability of such tissues and data can accelerate the discovery process of identifying novel biomarkers and therapeutic strategies for patients with prostate cancer.

Thus, a more comprehensive understanding of the tissue microenvironment at base line and following radiation therapy may inform improved strategies in radiation dosing, as well as complementary neoadjuvant and adjuvant treatments to achieve complete response in organ-confined disease in the future. Such an understanding of the tissue and biological response of prostate cancer to radiotherapy may also provide insights to enhance IR-based therapy of metastatic and oligometastatic disease, for both palliative and perhaps life-prolonging intent.

The primary goal of this tissue collection protocol is to establish a framework for the acquisition and banking of biospecimen collected from men undergoing brachytherapy. Biopsy of the prostate is an invasive procedure; however, in this tissue collection protocol, biopsies are acquired intraoperatively while patients are prepped for brachytherapy seed placement, thus minimizing the discomfort as well as the inconvenience of the biopsy procedure for patients. A subset of these patients will choose to have a 2 year confirmatory biopsy to detect the absence or persistence of disease. Biopsy cores collected 2 years post-IR therapy will also be included in the investigators' correlative studies. These biopsies will provide a valuable resource for molecular and pathological assessments. To extract the maximal amount of information from these biopsy specimens, the investigators will utilize comprehensive genomic, pathological, and biochemical analyses including DNA-seq, RNA-seq, methylome analysis, single cell sequencing, immunohistochemistry (IHC)/immunofluorescence (IF). The investigators will also collect and maintain a database of the clinicopathological parameters and follow up information for these specimens. The biobank will thus represent a bank of tissues as well as the correlative measurements on those tissues.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed prostate cancer within the past 12 months:
2. The patient has decided to undergo brachytherapy as treatment modality for his prostate cancer.
3. Suitable volume of disease for biopsy, defined as one or more of the following:

   1. Identifiable lesions of greater or equal to one
   2. Clinically palpable disease corresponding to (ipsilateral to) any involved core on biopsy OR
   3. ≥50% of biopsy cores involved with cancer
4. Patients or their legal representatives must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures.
5. Males 18 years of age or older
6. Signed study-specific consent form prior to registration

Exclusion Criteria:

1. Prior history of any other malignancy which was either newly diagnosed or recurred (following prior curative treatment) within last 2 years, other than non-melanoma skin carcinoma.
2. Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow up.

Primary outcomes:
measure: Acquisition and banking of biospecimen collected from men undergoing brachytherapy
timeFrame: Up to 2 years post-implant at confirmatory biopsy
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins SKCCC
name: Daniel Song, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. doi: 10.1016/s0140-6736(02)09408-4.
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