The main objective is to determine the maximum tolerated dose (MTD) that will be the recommended radiation dose for the phase 2 study, in which we intend on using a MR-guided boost after SCRT in patients with intermediate risk rectal cancer to…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the incidence of dose limiting toxicity, a composite
endpoint of (1) radiation toxicity grade >=4 according to Common Toxicity
Criteria for Adverse Events (CTCAE) version 5.0 occurring within 20 weeks after
start of radiotherapy and before surgery, (2) radiation toxicity grade 3
persisting > 12 weeks after start of radiotherapy, (3) postponing of surgery >
20 weeks after start of radiotherapy due to any grade of radiation toxicity and
(4) post-operative complications Clavien-Dindo IIIb-IV in residual disease
requiring surgery.
Secondary outcome
Secondary endpoints are technical feasibility of boost delivery, GTV coverage
of the boost fractions, non-dose limiting radiation toxicity and postoperative
complications, organ preservation rate, locoregional control, disease free
survival, overall survival, late radiation toxicity, quality of life (EORTC
QLQ-C30 and CR-29) and functional outcome (LARS, MFSQ, UDI-6 en IIQ, IIEF)
Background summary
Since recently, non-operative management is considered a possible treatment
option for patients with rectal cancer who reach a clinical complete response
(cCR) after neoadjuvant (chemo)radiotherapy. The chance of reaching cCR is,
among others, dependent on the neoadjuvant treatment schedule. For patients
with intermediate risk rectal cancer this schedule is short course radiotherapy
(SCRT). This scheme consists of 5 fractions of 5 Gy on the rectal tumor,
pathological lymph nodes and elective lymph node regions. Unfortunately, cCR
rates after SCRT seem to be only around 10%. As response after radiotherapy is
thought to be dose dependent, increasing the radiotherapy dose with SCRT
potentially will lead to more cCR and thereby more organ preservation
opportunities for these patients. However, there is only very limited
experience with dose escalation after 5x5 Gy and the safety of clinically
significant dose escalation is unclear.
Study objective
The main objective is to determine the maximum tolerated dose (MTD) that will
be the recommended radiation dose for the phase 2 study, in which we intend on
using a MR-guided boost after SCRT in patients with intermediate risk rectal
cancer to increase the chance for cCR. Secondary objectives are to determine
the feasibility, non-dose limiting toxicity, organ preservation rate,
oncological outcome and functional outcome, and to explore variables for early
response evaluation.
Study design
6+3 dose-escalation design with 4 radiotherapy dose levels.
Intervention
2, 3, 4, or 5 sequential, homogenous boost fractions of 5 Gy on the gross tumor
volume (GTV) in the week following SCRT using MR-guided online adaptive
radiotherapy on the MR-linac.
Study burden and risks
Benefits for patients may include higher probability of complete tumor response
that creates the opportunity for a watchful waiting strategy instead of
resection. Watchful waiting is expected to result in a higher quality of life.
Compared to standard treatment, the SCRT regimen including the sequential boost
will take 2 to 5 days extra in the week following SCRT. Possible risks include
higher radiation toxicity and surgical complication rates.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
primary intermediate risk rectal adenocarcinoma, fit for multimodal treatment
Exclusion criteria
contra-indication for magnetic resonance-guided treatment or for pelvic
radiotherapy (such as inflammatory bowel disease, prior pelvic radiotherapy,
pregnancy, hip implants)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL75671.041.21 |
| Other | NL8997 |
| OMON | NL-OMON22916 |