Clinical trial NCT03312972: Focal Salvage HDR Brachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy
Official title: F-SHARP: A Phase I/II Trial of Focal Salvage High-dose-rate BRachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Locally Recurrent Prostate Cancer
Keywords: Cancer
HDR Brachytherapy
Prostate Cancer
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2017-10-18
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This purpose of this study is to evaluate the safety and effectiveness of a technique called focal high-dose-rate (HDR) brachytherapy as treatment for prostate cancer that has come back in the prostate after prior radiotherapy. The study will examine the safety and efficacy of the treatment. The type of radiation that participants in this research will receive is targeted directly at the areas of the prostate where recurrent disease is evident, while avoiding treatment of the normal appearing prostate. This involves the placement of a radioactive material in the affected area of the prostate temporarily, where it remains for a short period of time, and then is subsequently removed using a minimally invasive technique called HDR Brachytherapy.

Detailed description: The goal of any radiation treatment plan is to achieve maximal disease response with minimal toxicity. HDR brachytherapy offers a promising definitive treatment option in the setting of Locally Recurrent Prostate Cancer after prior definitive radiation, based on the limited data described above, with achievement of biochemical disease control in a large percentage of patients with relatively low toxicity. With focal HDR brachytherapy, the investigators can treat the isolated areas of disease, while avoiding normal prostate tissue, with the goal of further improving toxicity rates. The investigators hypothesize that using single fraction, focal HDR brachytherapy performed with one single implant for the treatment of LRPC is feasible and without excess toxicity, and can be safely delivered. This should allow for better patient convenience and cost and improved treatment dosimetry and planning, as it will decrease the risk of catheter displacement between fractions, which will hopefully correlate to less GU and non-GU acute toxicity. The primary objective is to determine the acute and late GU and GI toxicity of single fraction focal HDR salvage brachytherapy (primary endpoint).

Eligibility criteria: Inclusion Criteria:

* Biopsy proven locally recurrent adenocarcinoma of the prostate after the completion of definitive radiation therapy for initially diagnosed prostate cancer.

  * Biopsy must be performed within 182 days of trial registration
  * Biopsy should be a standard sextant biopsy AND either a targeted MR/ultrasound guided biopsy or saturation biopsy or both.
* Initial cancer diagnosis that fits these specific criteria:

  * Stages T1-T3a
  * Nx or N0
  * Mx or M0
* Eligible initial definitive radiotherapy modalities include:
* External beam radiotherapy, with photon or proton beam therapy

  * Conventional or moderately hypofractionated radiotherapy
  * Extremely hypofractionated external beam radiotherapy (Stereotactic body radiation therapy)
* Definitive Brachytherapy:

  * Low-dose rate
  * High-dose rate
* Locally recurrent disease confined to the prostate +/- seminal vesicles and immediately adjacent tissue, as evaluated by the following:

  * History/Physical examination
  * Radiographically node negative disease (N0), as defined by CT or MR of pelvis +/- abdomen within 6 months of registration.
  * No evidence of bone metastases (M0) on bone scan within 6 months of registration.
  * Fluciclovine-PET is encouraged, but not required
* Patients receiving ADT are eligible as long as they meet the other eligibility criteria. However, the duration of all ADT must be documented.
* Current ECOG Performance status Scale 0-2
* Current International Prostate Symptom Score (IPSS) \< 20
* The patient must be medically suitable to receive general anesthesia.
* The patient must be able and willing to sign a study-specific written informed consent form before study entry.

Exclusion Criteria:

* Preregistration GI or GU toxicity (for any reason) grade ≥ 3 as defined in CTCAE version 4.03. That is, grade ≥ 3 GU or GI toxicity after first course of radiotherapy
* Patients receiving any other investigational agents.
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, severely symptomatic congestive heart failure, cardiac arrhythmia, recent myocardial infarction in last 6 months, or psychiatric illness/social situations that could limit compliance with study requirements.
* Patients who have received chemotherapy or immunotherapy within one month prior to study enrollment, other than ADT

Primary outcomes:
measure: Toxicity rate
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Charlottesville
country: United States
facility: University of Virginia School of Medicine
state: Virginia
Study officials:
affiliation: Loyola University
name: Abhishek Solanki, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parekh A, Graham PL, Nguyen PL. Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review. Semin Radiat Oncol. 2013 Jul;23(3):222-34. doi: 10.1016/j.semradonc.2013.01.006.
citation: Shipley WU, Thames HD, Sandler HM, Hanks GE, Zietman AL, Perez CA, Kuban DA, Hancock SL, Smith CD. Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. JAMA. 1999 May 5;281(17):1598-604. doi: 10.1001/jama.281.17.1598.
citation: Zelefsky MJ, Kuban DA, Levy LB, Potters L, Beyer DC, Blasko JC, Moran BJ, Ciezki JP, Zietman AL, Pisansky TM, Elshaikh M, Horwitz EM. Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):327-33. doi: 10.1016/j.ijrobp.2006.08.056. Epub 2006 Nov 2.
citation: Zumsteg ZS, Spratt DE, Romesser PB, Pei X, Zhang Z, Kollmeier M, McBride S, Yamada Y, Zelefsky MJ. Anatomical Patterns of Recurrence Following Biochemical Relapse in the Dose Escalation Era of External Beam Radiotherapy for Prostate Cancer. J Urol. 2015 Dec;194(6):1624-30. doi: 10.1016/j.juro.2015.06.100. Epub 2015 Jul 10.
citation: Ahmadi H, Daneshmand S. Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes. Patient Relat Outcome Meas. 2014 Jul 5;5:63-70. doi: 10.2147/PROM.S52788. eCollection 2014.
citation: Wirth MP, Hakenberg OW, Froehner M. Antiandrogens in the treatment of prostate cancer. Eur Urol. 2007 Feb;51(2):306-13; discussion 314. doi: 10.1016/j.eururo.2006.08.043. Epub 2006 Sep 11.
citation: Grado GL, Collins JM, Kriegshauser JS, Balch CS, Grado MM, Swanson GP, Larson TR, Wilkes MM, Navickis RJ. Salvage brachytherapy for localized prostate cancer after radiotherapy failure. Urology. 1999 Jan;53(1):2-10. doi: 10.1016/s0090-4295(98)00492-0.
citation: Beyer DC. Permanent brachytherapy as salvage treatment for recurrent prostate cancer. Urology. 1999 Nov;54(5):880-3. doi: 10.1016/s0090-4295(99)00241-1.
citation: Skowronek J. Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer - between options. J Contemp Brachytherapy. 2013 Mar;5(1):33-41. doi: 10.5114/jcb.2013.34342. Epub 2013 Mar 29.
citation: Grills IS, Martinez AA, Hollander M, Huang R, Goldman K, Chen PY, Gustafson GS. High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds. J Urol. 2004 Mar;171(3):1098-104. doi: 10.1097/01.ju.0000113299.34404.22.
citation: Yamada Y, Kollmeier MA, Pei X, Kan CC, Cohen GN, Donat SM, Cox BW, Zelefsky MJ. A Phase II study of salvage high-dose-rate brachytherapy for the treatment of locally recurrent prostate cancer after definitive external beam radiotherapy. Brachytherapy. 2014 Mar-Apr;13(2):111-6. doi: 10.1016/j.brachy.2013.11.005. Epub 2013 Dec 25.
citation: Chen CP, Weinberg V, Shinohara K, Roach M 3rd, Nash M, Gottschalk A, Chang AJ, Hsu IC. Salvage HDR brachytherapy for recurrent prostate cancer after previous definitive radiation therapy: 5-year outcomes. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):324-9. doi: 10.1016/j.ijrobp.2013.01.027. Epub 2013 Mar 6.
citation: Peters M, Maenhout M, van der Voort van Zyp JR, Moerland MA, Moman MR, Steuten LM, van Deursen MJ, van Vulpen M. Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: a retrospective study regarding toxicity, biochemical outcome and quality of life. Radiother Oncol. 2014 Jul;112(1):77-82. doi: 10.1016/j.radonc.2014.06.013. Epub 2014 Jul 3.
citation: Sasaki H, Kido M, Miki K, Kuruma H, Takahashi H, Aoki M, Egawa S. Salvage partial brachytherapy for prostate cancer recurrence after primary brachytherapy. Int J Urol. 2014 Jun;21(6):572-7. doi: 10.1111/iju.12373. Epub 2013 Dec 23.
citation: Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
citation: Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996 Dec;49(12):1373-9. doi: 10.1016/s0895-4356(96)00236-3.