Current studies on salvage radiotherapy (sRT) for biochemically recurrent prostate cancer
after radical prostatectomy investigate timing, dose-escalation and androgen deprivation
therapy (ADT) for recurrent prostate cancer. These approaches could either be limited by
radiation-related susceptibility of the anastomosis or by suspected side-effects of ADT. A
phase II protocol was developed to investigate the benefit and tolerability of regional
hyperthermia with moderately dose-escalated sRT. The study hypothesis is that hyperthermic
sRT is a safe and feasible salvage treatment modality. The primary endpoint is safety
measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events
(AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number
of hyperthermia treatments (n ≥ 7) and feasibility of sRT according to protocol. Target
volume delineation is performed according to the EORTC guidelines. sRT is administered with
single doses of 2 Gy 5×/week to a total dose of 70 Gy to the prostate bed, or alternatively
the total dose only to the area of highest risk and a lower dose to the remaining prostate
bed using a simultaneous boost (SIB) technique. Regional hyperthermia is given 2×/week to a
total of 10 treatments. German centres participate in the phase II trial using intensity
modulated RT (IMRT), volumetric modulated arc technique (VMAT) or tomotherapy. The initiating
centres were participants of the SAKK 09/10 study, where the same patient criteria and target
volume definition (mandatory successful performed dummy run) were applied insuring a high
standardisation of the study procedures.
The introduced phase II study implements modern sRT and regional hyperthermia. If the phase
II study is found to be safe and feasible, a multicenter phase III study might be performed
to test whether the addition of regional hyperthermia to dose-intensified sRT improves
biochemical control.
1. Lymph node negative adenocarcinoma of the prostate treated with radical prostatectomy
at least 12 weeks before randomization. Tumour stage pT2a-3b, R0-1, pN0 or cN0
according to the UICC TNM 2009; Gleason score available.
2. PSA progression after prostatectomy defined as two consecutive rises with the final
PSA > 0.1 ng/ml or three consecutive rises. The first value must be measured at least
4 weeks after radical prostatectomy.
3. PSA at randomization ≤ 2 ng/ml.
4. No evidence of macroscopic local recurrence or metastatic disease on pre-sRT-MRI
(magnetic resonance imaging; with i.v. contrast) or pre-sRT-CT (multislice computed
tomography with i.v. and oral contrast) of the abdomen and pelvis assessed within 16
weeks prior to randomization.
5. WHO performance status 0-1 at randomization.
6. Age at randomization between 18 and 80 years.
7. Informed consent.
Exclusion Criteria:
1. Persistent PSA value 4-20 weeks after radical prostatectomy > 0.4 ng/ml.
2. Palpable mass in the prostatic fossa, unless histology proves no evidence of
recurrence.
3. Pelvic lymph node enlargement >1 cm in short axis diameter of the abdomen and pelvis
(cN1), unless the enlarged lymph node is sampled and negative.
4. Presence or history of bone metastases. Bone scan is mandatory in cases of clinical
suspicion (e.g., bone pain).
5. Other malignancies within five years before planned sRT; non-melanoma skin cancers are
allowed.
6. ADT or bilateral orchiectomy.
7. Previous pelvic radiotherapy.
8. Hip prosthesis.
9. Metal clusters/markers and patients with a pacemaker.
10. Severe or active co-morbidities impairing the feasibility of hyperthermia or dose
intensified sRT including (but not exclusively limited to):
- chronic inflammatory bowel disease
- acute bacterial or fungal infection requiring intravenous antibiotics at the time
of randomization
- unstable angina pectoris and/or congestive heart failure requiring
hospitalization within the last 6 months
- transmural myocardial infarction within the last 6 months
- chronic obstructive pulmonary disease exacerbation or other respiratory disorders
requiring hospitalization or precluding planned treatment within the study at the
time of randomization
- psychiatric disorder precluding understanding of information on trial-related
topics, giving informed consent or filling out QoL questionnaires
11. Concurrent treatment with other experimental drugs or other anti-cancer therapy;
treatment in a clinical trial within 30 days prior to trial entry.
1. Acute grade 3+ adverse events (Time Frame - up to three months after end of treatment): Measured according to CTCAE version 4.
Secondary outcome:
1. Late adverse events (Time Frame - up to 36 months after end of treatment): According to CTCAE version 4.
2. Quality of life (QoL) assessment (Time Frame - up to 36 months after end of treatment): Using EORTC questionnaires
3. Biochemical progression-free survival (Time Frame - up to 36 months after end of treatment): PSA-rise > 0.4 ng/ml or increasing PSA-level where the initial PSA-level is above 0.4 ng/ml.
4. Clinical progression-free survival (Time Frame - up to 36 months after end of treatment): Occurrence of a local recurrence, regional recurrence or distant metastasis. Clinical progression-free survival is defined as the time between trial inclusion and occurrence of clinical progression, start of a new androgen deprivation therapy (see below) or death. Patients without event will be censored at the time of last follow-up.
5. Time without androgen deprivation therapy (ADT), i.e., time until initiation of ADT (Time Frame - up to 36 months after end of treatment): The time from trial inclusion until start of a new androgen deprivation therapy. Patients without new ADT will be censored at the time of last follow-up.
Regional Hyperthermia: Regional hyperthermia 1-2×/week to a total number of 7-10 treatments combined with salvage radiotherapy to a total dose of 70 Gy over 7 weeks
Quelle: ClinicalTrials.gov
Sie können folgenden Inhalt einem Kollegen empfehlen:
"Charité HT-Prostate"
Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.
Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!
