Clinical trial NCT01913717: Short-term High Precision Radiotherapy for Early Prostate Cancer With Concomitant Boost on the Dominant Lesion
Official title: Short-term High Precision Radiotherapy for Early Prostate Cancer With Concomitant Boost on the Dominant Lesion
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adenocarcinoma of Prostate
Keywords: Prostate cancer
Radiotherapy
hypofractionated radiotherapy
Lead sponsor: European Institute of Oncology
Sponsor class: OTHER
First posted: 2013-08-01
Enrollment: 65
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: The present research project aims to improve the current treatment for prostate-confined tumor, evaluating the safety and feasibility of a very short hypofractionated radiotherapy schedule administered with one of the best available dose delivery systems. The study will include 2 sub-studies (in-silica and clinical study) and 4 tasks.

Detailed description: Approximately 70% of men with newly diagnosed prostate cancer feature organ-confined disease. Conventional treatment options for prostate-confined cancer include radical prostatectomy, external beam radiation therapy, brachytherapy and active surveillance. All currently available treatments have comparable toxicity risk and high social and economic impact, hence the best treatment option has not been defined yet. In the radiation oncology field the gold standard for prostate cancer management is 7-8 weeks intensity modulated radiotherapy (IMRT), which can be delivered with the latest generation of accelerators providing modulated arc delivery (eg. RapidArc™, Varian) or with newly developed machines such as the Vero system (BrainLab AG - Mitsubishi Heavy Industries Ltd). The present research project aims to improve the current treatment for prostate confined tumor, evaluating the best strategy to deliver a very-short hypofractionated radiotherapy scheme. In the first part of this AIRC grant an in-silica study will be performed on 10 test prostate cancer patients, with comparative competitive treatment plans with the state of the art treatment options for prostate cancer: the Vero system, the RapidArc system, the Cyberknife (all available at the European Institute of Oncology IEO, Milan, Italy), and protontherapy (available at the Centre of Adrotherapy, in Pavia, Italy). This dosimetric comparison will be performed in order to define the technique that provides the maximum target coverage with the minimum dose to the surrounding organs at risk (OARs) to be used to perform the clinical trial that will follow within this AIRC grant. After performing the in-silica study, 65 newly diagnosed prostate cancer patients with 2011 National Comprehensive Cancer Network (NCCN) risk category ranging from very low to intermediate but not undergoing hormonal treatment, will be consecutively enrolled in a prospective phase II trial. The patients will be treated at the Division of Radiation Oncology of the IEO, with the dose delivery system that will result most fit at the in-silica study. Simultaneous Integrated Boost (SIB) technique will be applied to deliver a total dose of 36.25 Gy in 5 fractions (over 10 days) to the whole prostate (7.25 Gy/fraction) and 37.5 Gy to the dominant intraprostatic lesion DIL (7.5 Gy/fraction), profiting of the high sensibility of prostate cancer to high dose/fraction. Several strategies will be applied in order to reduce the dose to the surrounding OARs. In order to define the localization of the DIL, multiparametic magnetic resonance imaging (MRI) of the pelvis will be performed (with spectroscopy, diffusion weighted and perfusion acquisitions), and fused with computed tomography (CT) scan. In-room image-guidance will be applied at each treatment section, in order to minimize uncertainties in intra and inter-fraction prostate localization. At the end of the radiotherapy course, each patient will be followed-up, in order to assess the treatment safety and effectiveness in terms of early and late toxicity, and tumor control. A sampling from the prostate tumor tissue for biological study will be taken for microarray analysis. The expression of specific markers of radiosensitivity and radioresistance will be investigated.

Eligibility criteria: Inclusion Criteria:

- Histologically confirmed adenocarcinoma of prostate, including the following 2011 National Comprehensive Cancer Network (NCCN) risk categories: very low (T1c PSA \<10 ng/ml, Gleason score \<7, fewer than 3 positive biopsy cores, \<50% cancer in each core, PSA density \<0.15 ng/ml) or low (T1-T2a, PSA \<10 ng/ml, Gleason score \<7) or intermediate (T2b or T2c, PSA between 10 and 20 ng/ml, Gleason score of 7)

* cN0 and cM0 stage
* Age \> 18 years
* Good performance status (ECOG\< 2),
* No previous pelvic radiotherapy
* No previous prostatectomy
* No hormonal treatment (neoadjuvant or concomitant)
* No concomitant bowel inflammatory disease or other serious comorbidities
* Good urinary flow (peak flow \> 10 ml/s)
* No previous invasive cancer (within 5 years before the prostate cancer diagnosis) apart from non-melanoma skin malignancies.

Exclusion Criteria:

* Extraprostatic tumor extension (T3) or locally advanced disease (T4)
* Pelvic lymph node metastasis (N1)
* Distant metastasis (M1)
* Urinary obstructive symptoms (IPSS \> 20)
* Previous pelvic radiotherapy
* Severe systemic disorders
* Concomitant disorders including: chronic urinary or intestinal inflammatory conditions (for example, ulcerous recto-colitis, Crohn disease), anti-coagulant treatment (warfarin, heparin)
* Previous malignancy except for skin non-melanoma cancer or 3-year disease free interval from previous malignancy like in situ cervix cancer or non muscle invasive bladder cancer
* Non conformity of the radiotherapy dose distribution when compared to the dose constraints
* Psychiatric disorders or any other condition that can can make unreliable the informed consent

Primary outcomes:
measure: Acute toxicity
timeFrame: one month after radiotherapy
Secondary outcomes:
measure: late toxicity
timeFrame: 2 years
measure: efficacy of treatment
timeFrame: 2 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
Study officials:
affiliation: European Institute of Oncology
name: Roberto Orecchia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: European Institute of Oncology
name: BARBARA A JERECZEK, MD PhD
role: PRINCIPAL_INVESTIGATOR
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