Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04584008 |
| Other study ID # |
NGS01 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 23, 2020 |
| Est. completion date |
February 2024 |
Study information
| Verified date |
December 2023 |
| Source |
Peking University |
| Contact |
Lin Shen, MD |
| Phone |
86-10-88196561 |
| Email |
linshenpku[@]163.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This a prospective real-world navigation study using tumor DNA sequencing technology to
sequence genes of previously treated and refractory gastrointestinal tumors, which are
generally considered to be highly heterogeneous and complex, to screen potential molecular
targeted drugs for individualized treatment. This study may provide feasibility and response
information, which will be the basis for designing better randomized trials, which may change
the pattern of cancer treatment. If the hypothesis is finally proved, it will help doctors
and molecular biologists to choose the best drug (or combination of drugs) based on the
individual oncogenomics of each patient.
Description:
This is a prospective, open label, real-world study to evaluate the feasibility of matched
molecular targeted therapy in patients with refractory gastrointestinal cancer based on tumor
molecular characteristics as standard treatment failure. This is a non-randomized trial
designed to test molecular matching strategies based on patient genome information. The
molecular tumor board (MTB) will recommend treatment, but the treatment decision is up to the
attending physician. FoundationOne CDx was used for tissue genomic analysis. If possible,
PD-L1 immunohistochemistry (IHC), tumor mutation load (TMB), and microsatellite instability
(MSI) status will also be evaluated. Based on this information, MTB, composed of
multidisciplinary experts, will focus on the selection of customized, best matched drugs or
combinations to target most of the genomic changes in each patient, also taking into account
potential drug toxicity. The final treatment will be based on the choice of oncologists, who
will formulate treatment plan by combining MTB discussion, patient preference, attention to
complications, consideration of drug toxicity, insurance coverage of off label drugs and
availability of clinical trials of research drugs, thus reflecting the actual clinical
practice nowadays in China. The acquisition of drugs follows the actual situation in the real
world and is not within the scope of this study design.
The principles of MTB treatment recommendations can be referred to the NCI-MATCH trial:
Grade 1: FDA / NMPA approval; clear evidence and mechanism; concomitant diagnostic
relationship between drug and target.
Grade 2: The drug reaches the clinical end point (objective response rate, PFS or OS); there
is evidence of target inhibition; there is strong evidence to predict relationship between
the target and the drug.
Grade 3: The drug has evidence of clinical activity and target inhibition; there is some
evidence to predict the relationship between target and drug.
Grade 4: Pre-clinical evidence of anti-tumor activity and evidence of target inhibition;
there is hypothesis to predict the relationship between target and drug.
Patients who meet the inclusion criteria and sign informed consent will be analyzed for tumor
mutation by FoundationOne CDx detection. Biopsy specimens of metastatic foci can be selected
for gene detection. If there is no targeted therapy among patients, the archived diagnostic
tumor samples can also be used for detection. If the patient has received targeted therapy,
the investigators will try to obtain biopsy samples after treatment. If the sample cannot be
tested or the test results are not satisfactory, additional slices need to be sent to the
laboratory. If the repeated test fails, repeat biopsy if the clinical conditions permit, or
patients should be included in the unmatched treatment group.
Determining the interventability of gene mutations depends on genomic changes, allele
frequency, and diagnosis. This study will combine the recommendations of MTB and gene testing
reports to determine the interventability of mutated genes.
Interventional mutation: cancers have FDA or NMPA approved therapies, or there are matching
drugs in clinical trials.
Non-interventional mutation: there is no FDA or NMPA approved treatment for cancers, and no
matching drug is available in clinical trials.
MTB should at least be composed of attending doctors, molecular pathology experts and
bioinformatics experts. The research center is responsible for the establishment and holding
of MTB. As management of patients enrolled in this study is essential, the research
committee, including but not limited to the main investigator of the study and the treated
medical oncologist, can provide advice as needed between MTB meetings to avoid treatment
delays. By analyzing the genomic variation of patients, independent MTB recommends molecular
targeted therapy that can inhibit the mutation directly or through related pathways or be
included in relevant clinical trials. The independent research committee will use the
"N-to-1" model of precision medicine to propose a matching therapy consisting of at least one
drug that targets molecular changes. The investigators expect 50-70% of patients to carry
intervening variants, and that proportion is rising rapidly as learning more about these
pathways and drugs. The investigators expect that about 40% of patients with intervening
variants will be able to receive molecular targeted "matching" therapy.
