Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02125448 |
| Other study ID # |
NL42022.041.13 |
| Secondary ID |
PA13-0815 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 2013 |
| Est. completion date |
November 2016 |
Study information
| Verified date |
November 2020 |
| Source |
UMC Utrecht |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Rationale: For resectable esophageal cancer the standard therapy is 5 weeks of neoadjuvant
chemoradiotherapy (nCRT) followed by surgery 6-8 weeks afterwards. Surgery is performed
independent of the response to nCRT and is associated with substantial morbidity. A
pathological complete response (pCR) after nCRT is seen in 28-34% of patients. Pathological
non-responders (pNR) most probably do not benefit from nCRT but are exposed to its toxicity
and delay from surgical therapy inevitably occurs in this group. Early identification of
non-responders during nCRT would allow individualized decision making in continuation or
discontinuation of nCRT. Furthermore, a tool is desirable to accurately assess the treatment
response after nCRT to identify patients with a complete response. Studies in rectal cancer
reported that tumor resection could be omitted in patients with persisting clinical complete
response after 12 months. Also, in some esophageal cancer studies, complete responders in
surgical and non-surgical treatment groups had comparable overall survival. These findings
indicate the possibility to perform nCRT as sole treatment in patients with a complete
response. Conversely, if residual tumor is demonstrated, this will support the decision to
move to surgery.
Objective: Diagnostic study to assess the distinct and combined value of anatomical and
functional magnetic resonance imaging (MRI) and combined 18F-fluorodeoxyglucose positron
emission tomography and computed tomography (PET-CT) in the evaluation of treatment response
to nCRT for patients with esophageal cancer.
Study design: Multi-center diagnostic study investigating the value of MRI and PET-CT in the
imaging before, during and after nCRT for assessment of response to nCRT for resectable
esophageal cancer. Imaging response measurements will be compared with the histopathological
tumor regression grade (TRG) of the resection specimen as gold standard.
Study population: 50 patients (>18 years) presenting at the UMC Utrecht or M.D. Anderson
Cancer Center with resectable esophageal cancer, as determined by endoscopy and biopsy,
computed tomography (CT) and endoscopic ultrasonography (EUS), receiving nCRT prior to
surgery.
Procedure: In addition to the conventional diagnostic work-up for esophageal cancer including
a standard PET-CT before nCRT, two PET-CT scans will be performed during and after nCRT as
well as three MRI scans before, during and after nCRT at the same time points. The first MRI
(and standard-of-care PET-CT) scan session will be within the 6 weeks prior to the start of
nCRT. The second scan session will take place after 10-14 days after the start of nCRT. The
third and final scan session will be planned 1-2 weeks before surgery.
Main study parameters/endpoints: Determination of the distinct and combined diagnostic value
of anatomical and functional MRI and PET-CT in the evaluation of treatment response to nCRT
for patients with esophageal cancer. Important imaging parameters include apparent diffusion
coefficient (ADC) values, standardized uptake values (SUV) and volume measurements for the
different time points. The differences of these values between time points are of particular
interest (delta-ADC, delta-SUV, delta-volume). The sensitivity (%), specificity (%), negative
predictive value (%), positive predictive value (%), and accuracy (%) of the different
imaging parameters for correctly identifying histopathological complete response will be
calculated.
Description:
Multi-center diagnostic study investigating the distinct and combined value of MRI and PET-CT
for response prediction before and response assessment during and after nCRT for esophageal
cancer.
The patients will be enrolled in two hospitals (UMC Utrecht and M.D. Anderson Cancer Center)
during their first outpatient visit at the Department of Surgery or Radiation Oncology. At
the UMC Utrecht, for study purposes three anatomical and functional MRI scans are made and
two PET-CT scans, in addition to a pre-nCRT PET-CT scan which is standard care. At M.D.
Anderson Cancer Center, for study purposes three anatomical and functional MRI scans are made
and one PET-CT scans, in addition to a pre-nCRT and a post-nCRT PET-CT scan which are
standard care. The MRI scan protocol will consist of anatomical and functional MRI scans. For
the dynamic contrast-enhanced MRI (DCE-MRI) scans, a contrast agent will be administered to
the patient. All MRI scans will be performed on a 1.5-Tesla MRI scanner. For the PET-CT
scans, 18F-fluorodeoxyglucose (FDG) is the tracer that will be used for the assessment of
abnormal glucose metabolism in the tumor.
Before the start of nCRT, we schedule an MRIpre to have baseline MRI and PET-CT images in all
enrolled patients. This scanning day is matched to the irradiation treatment planning PET-CT
scan, which is routinely made for treatment planning purposes. Next, the patients receive
standard nCRT treatment with weekly administration of carboplatin (doses titrated to achieve
an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square
meter of body-surface area) for 5 weeks at UMC Utrecht and 6 weeks at M.D. Anderson Cancer
Center with concurrent radiotherapy (41.4 Gy in 23 fractions in Utrecht or 50.4 Gy in 28
fractions at M.D. Anderson, delivered 5 days per week on workdays). As mentioned in the
introduction, earlier studies reveal that both PET and DWI-MRI after 2 weeks of treatment
showed the best distinction between responders and non-responders. Therefore, we decided to
perform a PET-CTper and an MRIper scan two weeks after the start of the nCRT. Surgery will
follow 6-8 weeks after finishing nCRT and all patients will undergo a preoperative MRIpost
and PET-CTpost scan 1-2 weeks before surgery, combined with a standard preoperative
outpatient follow-up appointment. Overall, no extra hospital visits are asked from
participants as we try to schedule all study activities at days corresponding with
appointments for standard care. If in individual cases an extra visit to the hospital is
needed, travel expenses of this extra visit will be reimbursed.
Important imaging parameters include apparent diffusion coefficient (ADC) values,
standardized uptake values (SUV) and volume measurements for the different time points. The
differences of these values between time points are of particular interest (delta-ADC,
delta-SUV, delta-volume). The sensitivity (%), specificity (%), negative predictive value
(%), positive predictive value (%), and accuracy (%) of the different imaging parameters for
correctly identifying histopathological complete response will be calculated. The resection
specimen will be evaluated meticulously according to standard protocol (tumor type and
extension, lymph nodes, resection margins), and additionally, findings of effects of nCRT
will be reported.
The research population consists of patients with resectable esophageal carcinoma, scheduled
to receive preoperative chemoradiation according to the CROSS-regimen. The participants will
be recruited from the surgical outpatient clinic or radiation oncology department of the UMC
Utrecht or M.D. Anderson Cancer Center. In total 50 participants with available
histopathologic data of the resection specimen are required for this study.
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet
all of the following criteria (comparable with CROSS-criteria):
- Histologically confirmed squamous-cell carcinoma, adenocarcinoma or large-cell
undifferentiated carcinoma of the esophagus or esophagogastric junction (i.e. tumors
involving both cardia and esophagus on endoscopy)
- Potentially resectable tumor (cT1b-4a N0-3 M0): based on standard primary staging by EUS
and CT
- Undergoing preoperative chemoradiation according to CROSS-regimen
- Age>18 years
- No history of other cancer or previous radiotherapy or chemotherapy
- Signed informed consent
Exclusion criteria: A potential subject who meets any of the following criteria will be
excluded from participation in this study:
- Patients who meet exclusion criteria for MRI at 1.5T following the protocol of the
department of Radiology of the UMC Utrecht
- Patients who meet local exclusion criteria for intravenous contrast (Glomerular
Filtration Rate (GFR) of <45 mL/min/1.73m2, unless the patient has risk factors for
contrast nephropathy according to the UMC Utrecht protocol 'Prevention contrast reaction
and contrast nephropathy, Version 2 February 2012'). In patients with risk factors (2 or
more of the following: 'peripheral vascular disease, heart failure, age >75 years,
anemia, symptomatic hypotension, dehydration, use of diuretics or non-steroidal
anti-inflammatory drugs)', a minimum GFR of 60 mL/min/1.73m2 will be required
- Patients with insulin dependent diabetes mellitus or blood plasma glucose concentration
higher than 10 mmol/L
- Patients with a known Gadovist allergy
- Patients with a known CT-contrast allergy
- Patients having difficulty understanding Dutch
- Pregnant or breast-feeding patients
