The main goal of this phase II study is to investigate whether a focal ablative SBRT boost to the macroscopic tumor is feasible and associated with acceptable toxicity in addition to whole gland prostate SBRT. Based on the present study, a phase III…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Male genital tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints of this study are acute gastrointestinal (GI) and
genitourinary (GU) toxicity using the Common Terminology Criteria for Adverse
Events (CTCAE) version 4.0.
Secondary outcome
Secondary endpoints are late GI and GU toxicity, QoL, and bDFS. Simultaneously,
two side-studies will be performed, i.e. to prepare for MRI-guided radiotherapy
(except for Radboudumc and UZ Leuven) and blood sampling for translational
research (radiogenomics) and Biobank purposes (except for Radboudumc).
Background summary
Hypofractionation with a stereotactic body radiotherapy (SBRT) technique for
prostate cancer produces excellent treatment outcome in terms of survival and
toxicity and is much more convenient than the current fractionation scheme.
Local recurrence occurs most frequently at the site of the primary or dominant
tumor location prior to treatment. Therefore dose escalation at the site of the
primary tumor may improve disease control.
Study objective
The main goal of this phase II study is to investigate whether a focal ablative
SBRT boost to the macroscopic tumor is feasible and associated with acceptable
toxicity in addition to whole gland prostate SBRT. Based on the present study,
a phase III study will be designed to compare whole gland SBRT prostate and
whole gland SBRT prostate with an additional focal boost. The secondary
objectives of this study are: late toxicity, quality of life (QoL) and
biochemical disease free survival (bDFS).
Furthermore, two side-studies are incorporated in this phase II study: 1) a
weekly MRI will be performed to prepare for future MRI-guided (MR-linac)
treatment without gold fiducial markers (except for Radboudumc and UZ Leuven)
and 2) blood sampling for translational research (radiogenomics) and Biobank
purposes (except for Radboudumc).
Study design
Prospective interventional study on whole gland prostate SBRT using MRI for
focal boost in 100 consecutive intermediate or high risk prostate cancer
patients.
Intervention
Patients will be treated by external beam radiotherapy with a SBRT technique
with 35 Gy in 5 weekly fractions and an additional simultaneously integrated
focal boost to the tumor nodule(s) visible on MRI up to 50 Gy. In addition,
patients will be asked to undergo 5 additional MRI scans (~15 min/scan) without
contrast enhancement prior to or after each radiation session (except for
Radboudumc and UZ Leuven) as well as blood sampling for translational research
(radiogenomics) and Biobank purposes (except for Radboudumc).
Study burden and risks
Standard of care: Prior to radiation, patients in general visit the hospital 3
times for radiotherapy preparation; a first consultation visit with their
physician, gold fiducial marker implantation and pre-treatment imaging
(planning computed tomography (CT)-scan and magnetic resonance imaging
(MRI)-scan). Follow-up takes place according to standard of care. Patients will
be seen regularly for 10 years by their radiation oncologist and/or urologist.
Study procedures: The present study requires the same preparation for
radiotherapy treatment, but the radiation treatment involves only 5 fractions
in 5 weeks instead of the standard 28 to 35 fractions and is therefore much
more convenient.
Compelling data with sufficient follow-up are available on biochemical control
and toxicity for the SBRT protocol for 35-40 Gy in 5 fractions. In the present
study the macroscopic tumor will receive an additional radiation dose. Doses up
to 50 Gy in 5 fractions to the whole prostate have already been administered in
a phase II study with acceptable acute toxicity, but higher than acceptable
late rectal toxicity. Since in the current protocol only a small part of the
prostate volume receives an increased dose, unacceptable higher toxicity to the
organs at risk is not expected. This was confirmed in a phase II study using
Cyberknife. Furthermore, the dose constraints for the bladder and rectum will
be maintained as in the Canadian SBRT PATRIOT protocol (which were proven safe
and were associated with a very low rate of severe toxicity). To achieve equal
or less toxicity compared to the current radiotherapy protocols, the organs at
risk dose will be prioritised (i.e. the gross tumor volume (GTV) boost dose of
50 Gy will be adjusted to a lower dose if the dose constraints to organs at
risk are at risk). Toxicity and thus safety will be the primary endpoint of
this phase II study. Besides the standard toxicity assessments an additional
toxicity assessment will take place 3 months (± 1 maand) after the first
radiation treatment (by telephone or outpatient visit). QoL questionnaires will
be sent and returned by mail at baseline, at week 5 during treatment, at 1
month (± 2 weeks) and at 6 months (± 1 month) after the last radiation
treatment and every year (± 1 month) up to 5 year after the last radiation
treatment. Participating patients may benefit from this study since a reduced
number of 5 treatment fractions will be less disruptive to daily life than the
current 28 to 35 treatments.
For this study patients will also be asked to undergo 5 additional MRI scans
(~15min/scan) without contrast enhancement prior to or after each radiation
session (except for Radboudumc and UZ Leuven) as well as blood sampling for
translational research (radiogenomics) and Biobank purposes (except for
Radboudumc).
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Men >= 18 years with histologically confirmed prostate adenocarcinoma;
- Intermediate-risk prostate cancer or high-risk prostate cancer, defined as at least one of the following risk criteria:
* Clinical T-stage T2b, T2c or T3a (defined on MRI) or T3b with less than 5 mm invasion in the seminal vesicle.
* Gleason sum score >= 7.
* Prostate specific antigen (PSA) >= 10 ng/mL.
- Prostate tumor nodule visible on MRI;
- Ability to give written informed consent and willingness to return for follow-up.
Exclusion criteria
- Prior pelvic radiotherapy, transurethral prostate resection or prostatectomy;
- Unsafe to have gold fiducial marker implantation;
- Contraindications to MRI according to the Radiology Department guidelines (metal implants, non-compatible cardiac device, allergy to Gadolinium, severe renal dysfunction or severe claustrophobia);
- Evidence of lymph node involvement or distant metastatic disease;
- Clinical T-stage > T3b with >= 5 mm invasion in theseminal vesicle;
- World Health Organization (WHO) performance score > 2;
- International prostate symptoms score (IPSS) >= 15;
- PSA >30 ng/mL.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02853110 |
| CCMO | NL53719.041.15 |