To assess the impact of SBRT in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with mCRC.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Lead-in:
Feasibility, based on technical feasibility, logistical feasibility and patient
acceptance (details are provided in the protocol)
Phase II:
Progression free survival. Defined as the time from randomization until
progression of disease or death, whichever occurs first.
Secondary outcome
Lead-in:
Secondary outcome: Grade II adverse events of specific interest and grade
III/IV adverse events.
Phase II:
Overall survival, objective response rate of SBRT, time to disease related
treatment failure, health related quality of life, depth of response, pattern
of recurrence, treatment success rate, grade II adverse events of specific
interest and grade III/IV adverse events of SBRT and fatigue measurements by
MFI-20.
Background summary
In the Netherlands approximately 12.000 people per year are diagnosed with
colorectal cancer (CRC) of which 50% will develop distant metastases (mCRC). A
small number of CRC patients with limited metastases may be candidates for
local treatment of metastases (e.g., resection, ablation) with curative intent.
However, the majority of mCRC patients will not have this treatment option. The
standard treatment for these patients is palliative systemic treatment, of
which a benefit in overall survival has been demonstrated. The addition of
stereotactic body radiation therapy (SBRT) to metastases in a limited
unresectable metastatic setting might improve progression-free survival (PFS),
however is controversial. Two small proof of concept trials have demonstrated
positive effects in terms of survival and quality of life.
The success of the addition of local treatments in mCRC patients depends
largely on: control of microscopic disease, diagnostic accuracy of macroscopic
disease and effective treatment of all detected metastases with limited
additional toxicity to surrounding tissues. Until shortly, the use of SBRT was
possible to a limited number of locations due to target movement or toxicity to
surrounding radiosensitive structures. With the introduction of MRI-guided
radiotherapy these limitations have largely disappeared due to the possibility
to make a daily new treatment plan based on MRI-visualized anatomy. This allows
the use of smaller margins for uncertainty with less healthy tissues in the
radiation field. Thereby, a broader application of SBRT to add local control to
metastases became possible.
Study objective
To assess the impact of SBRT in combination with systemic therapy compared to
systemic therapy alone on safety and efficacy in patients with mCRC.
Study design
This study is an open-label, multicenter, randomized phase II screening trial
with a lead-in.
Intervention
SBRT on all metastatic sites followed by maintenance treatment.
Study burden and risks
It is hypothesized that systemic therapy and SBRT (experimental arm)
significantly improve the PFS of mCRC patients with locally untreatable
metastases compared to the current standard treatment of systemic therapy alone
(control arm). The most important potential burden/risks for patients allocated
in the experimental arm are: additional hospital visits for SBRT, which are one
preparation visit and one to four visits for treatment (dependent on locations
of metastases) and increased chance of adverse effects after SBRT. The
investigators expect that the potential overall PFS benefit of the experimental
arm outweighs the burden and risks of participation.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Histological proof of colorectal carcinoma (CRC)
- Colorectal metastatic disease
- Ten or less metastases as determined by the UCMU central review
- Stable disease or partial response after induction chemotherapy according to
RECIST 1.1 criteria
- Written informed consent
For all in- and exclusion criteria we want to refer to chapter 4 of the
protocol.
Exclusion criteria
- Possible treatment with curative intent according to local tumor board
- Substantial overlap with a previously treated radiation volume. Previous
radiotherapy is allowed as long as the composite plan meets dose constraints
herein.
- Contra-indication MR-LINAC (pacemaker or implantable
cardioverter-defibrillator)
For all in- and exclusion criteria we want to refer to chapter 4 of the
protocol.
Design
Recruitment
Medical products/devices used
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 | NCT05375708 |
| CCMO | NL76444.041.21 |