The main objective of this study is to determine the maximum tolerated dose (MTD) of 2-fraction boost MRI-guided radiotherapy (MRgRT) for patients with SCC following CROSS therapy. The secondary objectives are feasibility, non-dose limiting toxicity…
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
primary endpoint is the incidence of a dose limiting toxicity (DLT). Early DLT
is defined as radiation induced esophageal fistula/ perforation/ hemorrhage/
necrosis or tracheal, bronchial or bronchopleural fistula/tracheal or
bronchopulmonary hemorrhage grade >= 3 or any non-hematological grade 4 toxicity
according to Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0
occurring within 16 weeks after the start of radiotherapy and before surgery or
the postponing of surgery > 16 weeks after the end of radiotherapy due to any
grade of treatment-related toxicity. Subacute DLT is defined as peri- and/or
postoperative complications occurring within 30 days after surgery, defined as
postoperative anastomotic leakage or pneumonitis >= 3b according to
Clavien-Dindo
Secondary outcome
Secondary endpoints are non-DLT toxicity, the technical feasibility of dose
delivery, perioperative complications, and oncological outcomes including R0
resection rate, histopathological tumor response, local and regional recurrence
and death from any cause.
Background summary
Esophageal cancer (EC) is the seventh most frequently diagnosed cancer and the
sixth leading cause of cancer-related death worldwide. As a result of the late
onset of symptoms, most patients with EC present in an advanced stage with a
corresponding poor prognosis. Poor disease outcome after surgery alone (5-yr
overall survival between 25-40%) prompted many researchers to explore
neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant or perioperative
chemotherapy (nCT/pCT) approaches. nCRT has led to pathological complete
response (pCR) rate in squamous cell EC of almost 50%. Patients with a pCR have
a favorable prognosis with 5-year OS >50%. In addition, patients who will
achieve a pCR might be candidates for an organ preserving treatment strategy.
Current standard nCRT consists of a relatively low dose of radiation compared
to other tumors in the same area. We hypothesize that increasing the dose of
radiation will lead to increased local tumor control and pCR rates.
Study objective
The main objective of this study is to determine the maximum tolerated dose
(MTD) of 2-fraction boost MRI-guided radiotherapy (MRgRT) for patients with SCC
following CROSS therapy. The secondary objectives are feasibility, non-dose
limiting toxicity, oncological outcomes and to explore variables for early
response evaluation.
Study design
6+3 dose-escalation design with 3 radiotherapy dose levels
Intervention
2 sequential, homogenous boost fractions of 4-7 Gy on the gross tumor volume
(GTV) in the week following CROSS using MR-guided online adaptive radiotherapy
on the MR-linac. Start in dose level 0, of 2 x 5Gy boost per patient, and if
safe this is increased step-wise to a maximum dose level 2 of 2 x 7Gy per
patient.
Study burden and risks
The benefits for the patients may include higher probability of complete
pathological response that initially leads to increased survival and could
eventually result in organ-sparing treatment programs. Compared to standard
treatment, the CROSS regimen including the sequential boost will take 2 days
extra in the final week of CROSS. Possible risks include higher radiation
toxicity and surgical complication rates. However, we expect this increase to
be minor, for we will use dose constraints on organs at risk, which are
associated with low radiation-induced toxicity, and they will not be exceeded.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
Patients with squamous cell carcinoma of the esophagus or gastroesophageal
junction (Siewert I or II), potentially resectable tumor , eligible for
neoadjuvant CROSS chemoradiotherapy, age >= 18 years, WHO performance status
0-2.
Exclusion criteria
Adenocarcinoma, non-resectable, inoperable or metastatic squamous cell cancer
of the esophagus or gastroesophageal junction, prior radiotherapy to the
mediastinum, pregnant or breastfeeding patients.
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 |
|---|---|
| CCMO | NL86456.041.24 |