To determine the effect upon progression free survival and upon tumourload relative to baseline, both at one year after randomisation of immediate SABR versus delayed SABR (a scan-and-personalise policy). Secondarily, patterns of progression,…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary: Rate of progression free survival at one year; tumourload at one year
(relative to baseline).
Secondary outcome
- Relative change of tumourload at one year after randomisation expressed as
volume of all tumour at one year divided by volume of all tumour at time of
randomisation;
- Time to failure of local strategy (TFLS): failure = death or progressive
disease NOT amenable to local treatment;
- Progression of target lesions and progression outside of target lesions at
one year;
- Health-related quality of life (EURO QOL5), pulmonary symptoms
(EORTC-QLQ-LC13), and emotional distress (Hospital Anxiety and Depression
Scale, HADS).
Background summary
SABR (Stereotactic ablative radiotherapy) is one of the standard treatment
options besides surgical resection for limited lung metastases
(oligometastases) from colorectal cancer. High efficacy in terms of local
control of metastatic lesions treated has been shown. Nevertheless, the precise
effect of SABR upon progression-free- and overall survival in these patients is
unknown. To further evaluate and develop local treatment options in metastatic
disease, more information is necessary regarding the impact upon * and the
pattern of * disease progression of local treatment options such as SABR.
Study objective
To determine the effect upon progression free survival and upon tumourload
relative to baseline, both at one year after randomisation of immediate SABR
versus delayed SABR (a scan-and-personalise policy). Secondarily, patterns of
progression, patient-reported symptoms and quality of life will be monitored.
Study design
Randomised phase II clinical study.
Intervention
Randomisation (1:1) between immediate SABR versus delayed SABR (delayed =
treatment six months after randomisation or at disease progression, whichever
comes first).
Study burden and risks
SABR besides surgical metastasectomy is considered as treatment option for
patients with limited metastases from colorectal cancer that are technically
amenable for local treatment. SABR is a safe (no mortality) and little
burdensome treatment that is frequently administered to patients with
metastases from various solid tumours outside clinical studies. Although high
rates of local control have been shown in case series and single-arm studies,
there are no studies investigating the optimal role of SABR in the management
of the patient with oligometastatic stage disease. There is also no definitive
information about comparative effectiveness of SABR versus surgical
metastatsectomy.
One of the major open questions is the optimal point in time to administer SABR
(early, or rather later).
Patients participating in the present study might theoretically have a 50%
chance of benefit from participation in case they are randomised to the
delayed-SABR (scan-and-personalise) arm, if they happen to harbour diffusely
spreading disease that is not obvious at the time of considering participation,
but at 3 or 6 months follow-up. In that case they might be spared unnecessary
local treatment such as SABR, if they happen to get randomised into the
experimental arm; they will in this case directly be considered for systemic
treatment.
The risk of missing the stage of treatability by deferring treatment in the
experimental arm (scan-and-personalise) is estimated to be minimal because of
tumour biological facts: one tumour doubling time frequently equals about the
interval to the first CT scan (3 months) with the possibility to initiate SABR
(or other local treatment) at that time if appropriate. One
tumour-volume-doubling is equal to a 25% increase in diameter, i.e., the
largest tumour eligible for the study (30mm) will have grown to a still
treatable diameter of 38mm.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
- Age * 18 years
- WHO-PS 0 * 1.
- Patients with 1 to 3 lung metastases between 8 mm and 3 cm each, from colorectal cancer.
Resection has been considered at a multidisciplinary conference but was not recommended or
has been refused by the patient.
- Possibility to define target lesions that fulfil the following criteria:
* No lesion larger than 3 cm;
* Not more than 3 metastases * 8 mm in total (lesions smaller than 8 mm in diameter are NOT
counted and will NOT be irradiated);
- No prior radiotherapy (SABR or other) within about 2 cm from target lesions (i.e., the distance
between prior PTV to actual intended PTV is more than 2 cm AND dose distribution of former
radiation permits SABR).
- Primary tumour has been completely removed surgically.
- Metastases outside target organs (e.g. livermetastases or other) are radically treated locally
(resection, RFA, MWA, stereotactic radiotherapy, or other). Earlier resected or ablated (SABR,
RFA, MWA) metastases to lung, liver, or other organ form no exclusion criterion. Brain
metastases should be completely resected or treated with stereotactic radiosurgery. Bone
metastases should be resected or treated with high dose radiotherapy (equivalent of > 40 Gy)
and be asymptomatic.
- Patients at reproductive potential must agree to practice an effective contraceptive method.
Women of childbearing potential must not be pregnant or lactating.
- Proficiency in the Dutch language so that quality-of-life questionnaires can be completed in
Dutch and absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule; those
conditions should be discussed with the patient before registration in the trial.
- Before patient randomisation, informed consent must be given according to ICH/EU GCP
(International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH); EU: European Union; GCP: Good clinical practice), and
national/local regulations.
Exclusion criteria
- Any clinical symptoms possibly or certainly caused by index lungmetastases
- Physical inability to undergo stereotactic radiotherapy (e.g., serious shoulder stiffness)
- Any uncontrolled malignancy other than index colorectal cancer
- Other malignancy within recent two years, even if completely under control (under control = no evidence of disease)
- Failure to comply with any of the inclusion criteria.
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 | NCT02414334 |
| CCMO | NL53079.042.15 |