Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03616951 |
| Other study ID # |
151115 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2018 |
| Est. completion date |
January 1, 2024 |
Study information
| Verified date |
April 2020 |
| Source |
University of Aarhus |
| Contact |
Frede Donskov, MD, DMSc, associate professor |
| Phone |
+ 45 40465234 |
| Email |
frede.donskov[@]auh.rm.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The incidence of renal cancer in Denmark is approximately 900 new cases per year. Untreated,
the 5-year survival rate for metastatic renal cancer (mRCC) is 2%. Development of
angiogenesis inhibitors (AI) and check-point immunotherapy (CPI) has improved survival.
Treatment efficacy is evaluated by CT scans, using RESIST 1.1 (Response Evaluation Criteria
in Solid Tumors). However, progressin in patients with mRCC treated with AI or CPI is
difficult to characterize at the right time, using the RECIST 1.1. Therefore approximately 50
% of the patients are 'lost' to further treatment at the time of progression and die.
The investigators aim to evaluate if functional imaging parameters using spectral
CT-techniques can detect treatment failure earlier, or more accurate, than routine CT. This
could help us develop a new set of response evaluation criteria for functional imaging,
giving a more precise assessment of treatment effect in patients with mRCC treated with AI
and CPI.
Description:
Response evaluation criteria in metastatic renal cell carcinoma: Improved assessment of
response and progression by Spectral CT?
Clinical Background
Renal cancer accounts for 2-3% of all cancers. The incidence of renal cancer in Denmark is
approximately 900 new cases per year. Renal cell carcinoma (RCC) arises from the renal
parenchyma and is by far the most common type. In 20-30% of all new cases, metastases exist
at the time of diagnosis. Up to 25-50 % of patients treated with nephrectomy for localized
RCC will eventually develop metastases. Untreated, the 5-year survival rate for metastatic
RCC (mRCC) is 2%, and the median survival is 3 months. Within the last 10 years, an increased
understanding of kidney cancer biology, and the immune system, has resulted in the
development and approval of more than 12 new biological drugs. These are characterized by
inhibiting the formation of new blood vessels (angiogenesis inhibitors) or by activating the
patient's own immune system to attack the cancer disease (check-point inhibitors). Survival
has significantly improved for the patient group with these drugs. The treatment results in
control of tumor growth in the majority of patients, for a certain length of time, but should
be given continuously, has side effects, and is expensive. In case of disease progression,
treatment is changed to another drug. Thus, treatment for mRCC comprises sequential
alternating drugs for as long as possible. However, progression is difficult to characterize
at the right time and approximately 50 % of the patients are 'lost' to further treatment at
the time of progression and die. The investigators therefore need improved diagnostic tools
for early or more accurate detection of treatment failure, resulting in appropriate change of
therapy at the right time. Routinely, treatment efficacy is evaluated by CT scans at baseline
and every 3 months, using the criteria laid out in RECIST 1.1 (Response Evaluation Criteria
In Solid Tumors). When interpreting the CT scan, the sizes of target lesions are measured,
and an increase in the sum of target lesions by 30%, or the appearance of a new lesion, are
interpreted as disease progression. However, the size of the tumor does not necessarily
represent biological and physiological changes within the tumor; Tumors treated with
angiogenesis inhibitors may show little or no change in tumor size, or may enlarge slowly
during therapy, in spite of clinical benefit to the patient and extended time-to-progression.
New lesions or tumor enlargement may be seen as part of pseudo-progression in patients
treated with check-point inhibitors.
Therefore, the criteria from RECIST 1.1, despite being the best available at the moment, are
far from an optimal tool for evaluating response and progression in patients with mRCC
treated with biological therapy.
Recent studies from the research group behind the current pH.D. project have shown that
functional imaging with Dynamic Contrast Enhanced Computer Tomography (DCE-CT) was able to
measure changes in blood flow over time in a single metastasis. Using DCE-CT, the best
clinical effect of angiogenesis inhibitor therapy was seen in patients with the greatest
decline in blood volume and blood flow, measured after 1 month of treatment compared with
baseline. In contrast, patients with low blood volume and low blood flow at baseline had the
worst survival, with almost no benefit from treatment, regardless of whether they were
treated with angiogenesis inhibitors or immunotherapy.
Based on these results, functional imaging using DCE-CT has the potential to serve as a
predictive and prognostic tool in patients with mRCC. However, the DCE-CT technique can only
measure functional parameters in one single metastasis and requires use of extra intravenous
contrast, and increases radiation dose to the patient.
A new technique, Spectral CT, can visualize and measure functional parameters in all
metastases in the body, with use of no extra intravenous contrast, and with no extra
radiation dose compared to conventional CT. Spectral CT can quantify parameters such as
iodine density and iodine concentration - parameters that could be associated with blood flow
and blood volume - and also the relative atomic number can be measured. Response evaluation
criteria in metastatic renal cell carcinoma: Improved assessment of response and progression
by advanced CT-techniques?
Technical background
Spectral-CT adds spectral resolution to traditional CT scans through a new dual-layer
spectral detector. With an Yttrium-based scintillator, the NanoPanel prism detector
identifies high-energy and low-energy photons simultaneously, allowing not only anatomy, but
also color to characterize the material's content of structures. This new technique allows
the characterization of the metastases with parameters such as: iodine density, iodine
concentration and the relative atomic number. Spectral CT uses iodinated contrast media -in
the same dose as conventional CT. The amount of radiation in a Spectral CT is the same as in
a conventional CT.
Aims and hypothesis The present study aims to evaluate functional imaging Spectral-CT as
means to improve evaluation of response and progression in patients with mRCC.
The aim is to examine the correlation between Spectral-CT parameters and outcome in patients
with mRCC treated with angiogenesis inhibitors and check-point inhibitor immunotherapy.
- Spectral-CT parameters at baseline have predictive and prognostic value, and spectral CT
parameters during treatment are more accurate than RECIST 1.1 in determining response and
progression.
Materials and Methods The project is an explorative prospective study, in which the
investigators will examine the correlation between Spectral-CT functional imaging parameters
and outcome in patients with mRCC treated with angiogenesis inhibitors and immunotherapy. CT
will be performed at baseline, after 1 and 3 months and then every 3 months until progression
or death. CT will be performed using the Spectral IQON scanner from Philips, from which the
investigators will receive routine CT images, but also Spectral CT-images. In this way the
patients can be their own control. The investigators plan to include 60 patients.
Endpoints and data processing In order to evaluate the accuracy of Spectral-CT imaging, the
clinical endpoints best response, progression-free survival (PFS) and overall survival (OS)
will be used.
Patient registry
Following patient information will be collected from the patients medical record og
registered:
- Demographic data (date of birth, height, weight)
- Information about surgical and non-surgical treatment of renal cell carcinoma
- The patients list of medication
- Localisation of primary tumor and metastasis
- Histological parameters
- Findings on radiological examinations
- Blood tests: hemoglobin, white blood cell count, leucocytes, thrombocytes, creatinin,
natrium, potassium, bilirubin, alanine transaminase, alkaline phosphatase, lactate
dehydrogenase,calcium, albumine.
- Information about oncologic treatment after the patient progresses in actual study
Ethical Considerations The "Spectral-CT" study is approved by The Central Denmark Region
Committees on Health Research Ethics (journal no. 1-10-72-242-17) and is approved the Data
Protection Agency (journal no. 1-16-02-791-17). No procedure in the study will be performed
before written informed consent has been obtained from each patient.
4. Perspectives Functional imaging using DCE and Spectral CT is considered a potential, new,
non-invasive biomarker with the potential to serve as a predictive and prognostic tool.
Biomarkers have traditionally been developed by analyzing blood or biopsy material.
Core-needle tumor biopsies are, however, invasive procedures with associated discomfort and
complications. The development of a non-invasive biomarker, obtained at the same time as
routine CT assessment, which has potential for treatment selection (predictive tool) and
improved prognostication, would therefore be a significant advance for patient with mRCC. To
our knowledge no previous studies have investigated he correlation between DCE-CT parameters
and the amount of blood vessels in tumor biopsies. Nor have Spectral CT been used as
evaluation of response and progression in mRCC patients. The present study has the potential
to develop an updated RECIST - integrating tumor size with functional information. This could
give a more precise assessment of oncological treatment, thereby improving patient care.
