Trial Information

Stereotactic Body Radiation Therapy for cT1c - cT3a Prostate Cancer With a Low Risk of Nodal Metastases (≤ 20%, Roach Index): a Novalis Circle Phase II Prospective Randomized Trial

This protocol presents a randomised phase II study aiming to investigate the tolerance and
disease control of extreme hypofractionated RT for prostate cancer by delivering 5 x 7.25 Gy
= 36.25 Gy over two alternative time schedules: either over 9 days (study A), or over 28
days once-a-week, the same week-day (study B).

The total dose and fractionation schedules have been chosen based on the assumption of their
isoeffectivity regarding potential late rectal effects to be expected with a maximum
equivalent dose of 74 Gy in 2 Gy fractions and assuming an alpha/beta = 3 Gy for the rectum.

In both arms, the prescribed dose per fraction to the urethra and the surrounding
transitional zone will be dropped from 7.25 Gy to 6.5 Gy with a simultaneous integrated
boost (SIB) technique. A dose of 5 x 6.5 Gy is equivalent to 31 x 2 Gy assuming an
alpha/beta = 3 Gy for the urethra and equivalent to 37 x 2 Gy assuming an alpha/beta = 1.5
Gy for microscopic tumour foci in the transitional zone surrounding the urethra. The two
treatment regimens chosen will each be the object of a separate phase I-II study covered by
the same protocol and performed in parallel by the participating centres. Randomised
assignment to either of the two studies will be introduced to avoid selection bias in
treatment assignment within each centre.

OBJECTIVES:

Primary

- To determine the risk of urinary, rectal and sexual acute and late toxicities rates in
patients receiving two different time schedules of extreme hypofractionated radiation
therapy

• Secondary

- To determine the Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25)
in patients receiving two different time schedules of extreme hypofractionated
radiation therapy

- To determine the rate of local failure

- To determine in the two study arms the biochemical disease-free survival bDFS rate

- To determine in the two study arms the metastases-free survival rate

- To determine in the two study arms the disease-specific survival rate

OUTLINE:

This is a multicenter study.

Patients undergo extreme hypofractionated radiation therapy for prostate cancer by
delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules:

Experimental Arm A: Over 9 days. Experimental Arm B: Over 28 days once-a-week, the same
week-day. All patients will be followed up for at least 18 months to contribute to the
analysis of the main endpoints of the study. With reference to the secondary endpoints,
follow-up will be extended to 10 years.

Stopping rule: In order to avoid exposure of patients to a treatment that may be unsafe,
acute GI and GU toxicity will be continuously monitored with the purpose of assisting in the
decision of possibly interrupt recruitment in case of an alarming frequency.To this purpose,
the procedure of Ivanova et al., 2005 will be applied.