Clinical trial NCT01839994: Conformal Radiotherapy (CRT) Alone Versus CRT Combined With HDR BT or Stereotactic Body Radiotherapy for Prostate Cancer
Official title: Phase III Clinical Trial on Conventionally Fractionated Conformal Radiotherapy (CF-CRT) Versus CF-CRT Combined With High-dose-rate Brachytherapy or Stereotactic Body Radiotherapy for Intermediate and High-risk Prostate Cancer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: prostate cancer,
high-dose-rate brachytherapy boost,
stereotactic body radiotherapy boost,
conformal radiotherapy,
randomized trial
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2013-04-25
Enrollment: 350
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the outcomes of conventionally fractionated conformal radiotherapy with CF-CRT combined with either high-dose-rate brachytherapy or stereotactic body radiotherapy for intermediate or high-risk prostate cancer patients.

Detailed description: Prostate cancer is considered as a disease with relatively slow natural course and good clinical prognosis. Such description, however, does not well refer to intermediate and high-risk cases where long-term rate of biochemical progression remains not satisfactory, and the available treatment modalities entail a considerable morbidity. Over the last decade several competitive therapeutic approaches have evolved in curative treatment for intermediate and high-risk prostate cancer. The use of intensity-modulated radiation therapy (IMRT) made possible to escalate the total dose to the prostate without excessive toxicity.

Based on assumption of low value of low α/β value for adenocarcinoma of prostate, there is a potential of escalating the biological dose to the tumor with higher dose per fraction. High-dose-rate brachytherapy (HDR-BT) is one of the options, with the ability to conform radiation dose to the prostate with sharp dose gradient adjacent to critical organs. An increasing number of studies suggest its usefulness as a boost in intermediate and high risk disease. The randomized trial conducted in UK compared external beam radiotherapy (EBRT) alone with EBRT and HDR brachytherapy as a boost. Combining EBRT with HDR BT - boost resulted in significantly higher relapse-free-survival (RFS) with comparable incidence of severe late toxicity. However, the total dose used in EBRT alone - arm and radiotherapy technique may be considered suboptimal according to current standards.

Stereotactic body radiotherapy (SBRT) may be an interesting alternative to HDR brachytherapy, not requiring implantation of multiple catheters and anesthesia. SBRT boost for advanced localized prostate cancer has the potential to reduce toxicity while escalating the dose. First results of trials combining conventional irradiation with hypofractionated stereotactic boost and institutional pilot results gave promising outcome.

The comparison of these modalities of radiation therapy for prostate cancer will be performed in the current phase III trial study.

Eligibility criteria: Inclusion Criteria:

1. Pathologically proven adenocarcinoma of the prostate
2. Clinical stage T1-T3a (Intermediate or high risk features according to NCCN criteria)
3. No evidence of nodal or distant spread as determined by chest X-ray, bone scan and abdominal ultrasound or CT-scan or other investigations such as Positron Emission Tomography \[PET\] scan if required
4. No evidence of bulky spread beyond the capsule of the prostate, no seminal vesicle involvement assessed by TRUS or MRI of pelvis.
5. Good performance status (ZUBROD \<2, Karnofsky index \>=80%).
6. No contradictions for spinal anesthesia.
7. No contradictions for hormonal treatment (androgen deprivation).
8. Adequate bone marrow, renal and liver function.
9. Life expectancy in excess of 5 years.
10. No prior malignancy, except basal or squamous cell skin cancer.
11. Informed consent for participation in the study (confirmed by the signature together with the standard medical consent form for radiotherapy within the pelvis)

Exclusion Criteria:

1. Different histology than adenocarcinoma.
2. Previous or concurrent malignancy, with the exception of basal cell carcinoma of the skin.
3. Locally advanced disease: bulky T3a and/or T3b.
4. Presence of metastatic disease (nodal and/or distant).
5. PSA \>100ng/ml
6. Any previous therapy other than hormonal treatment.
7. Concurrent uncontrolled medical conditions.
8. Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
9. Withdrawal of informed consent.

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Primary outcomes:
measure: Freedom from biochemical failure (FFBF)
timeFrame: 3 years
Secondary outcomes:
measure: Freedom from local relapse
timeFrame: 3 years
measure: Freedom from loco-regional relapse
timeFrame: 3 years
measure: Freedom from distant metastases
timeFrame: 3 years
measure: Time of occurrence, incidence and severity of acute normal tissue reactions as measured according to CTCAE v4.0 and RTOG/EORTC scoring system
timeFrame: 3 months
measure: Time of occurrence, incidence and severity late normal tissue reactions as measured according to CTCAE v4.0 and RTOG/EORTC scoring system
timeFrame: 3 years
measure: Overall survival
timeFrame: 5 years
measure: Progression-free survival
timeFrame: 3 years
Other outcomes:
measure: Identification of molecular and biochemical predictors of response to external beam radiotherapy and brachytherapy or SBRT boost as compared to external beam radiotherapy alone
timeFrame: 3 years
Locations:
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch
state: Silesia
Study officials:
affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland
name: Rafał Suwiński, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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