Trial Title:
Multi-omics Sequencing in Neoadjuvant Immunotherapy of Gastrointestinal Tumors
NCT ID:
NCT05515796
Condition:
Immunotherapy
Gastric Cancer
Rectal Cancer
Chemotherapy Effect
Radiotherapy
Conditions: Official terms:
Stomach Neoplasms
Rectal Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Trastuzumab
Tislelizumab
Conditions: Keywords:
Immunotherapy
Gastric Cancer
Rectal Cancer
neoadjuvant
Terelizumab (aka Tislelizumab)
radiotherapy
oxaliplatin
capecitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative)（n=80） Gastric
cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )（n=20） Rectal
cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)（n=100）
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Terelizumab (aka Tislelizumab)
Description:
q3w Terelizumab (aka Tislelizumab) 200mg on day 1 of each cycle
Arm group label:
Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative)
Arm group label:
Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )
Arm group label:
Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)
Intervention type:
Drug
Intervention name:
CapeOx
Description:
Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine:Dose of 1000mg/m2,14days
Arm group label:
Gastric cancer:CapeOx+Terelizumab (aka Tislelizumab)(HER2 negative)
Arm group label:
Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )
Arm group label:
Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
q3w Trastuzumab (6 mg/kg following an initial loading dose of 8 mg/kg) on day 1 of each
cycle
Arm group label:
Gastric cancer:CapeOx+Trastuzumab+Terelizumab (aka Tislelizumab) (HER2 positive )
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
25 Gy/5 fractions
Arm group label:
Rectal cancer:Radiotherapy with CapeOx+ Terelizumab (aka Tislelizumab)
Summary:
immunotherapy，gastric cancer，rectal cancer，biomark
Detailed description:
To investigate the effect of Terelizumab (aka Tislelizumab) combined with XELOX in
Neoadjuvant Therapy for gastrointestinal tumors.
To explore new biomarkers that can predict the efficacy of combined immunotherapy, and to
establish a clinical efficacy prediction model by means of bioinformatics to
prospectively judge the efficacy and guide the follow-up individualized and accurate
treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The patients are able to understand and voluntarily sign the written informed
consent, which must be signed prior to the implementation of the designated research
procedures required by the study.
- The age at the time of signing the informed consent form (ICF) is ≥ 18 years old,
both male and female.
- Locally advanced or metastatic gastric / gastroesophageal junction adenocarcinoma
(clinical stage ≥ T2N0M0) and pMMR/MSS(tumor biopsy immunohistochemical identified
pMMR or next generation sequencing identified MSS) locally advanced rectal
adenocarcinoma (clinical stage T3-4N0M0 or T1-4N+M0 ) were diagnosed by
comprehensive evaluation.
- The patients are willing to provide fresh tissue for biomarker analysis, and the
tissue samples provided are of sufficient quality to evaluate the status of
biomarkers. If sufficient tissue is not provided, repeated sampling may be required.
- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)
score of 0 or 1.
- The expected survival time was ≥ 3 months.
- The patient has adequate organs function
1. The patient has adequate hematologic function, as evidenced by an absolute
neutrophil count (ANC) ≥1.5*10^9/L, hemoglobin ≥90g/L (5.58 mmol/L), and
platelets ≥100*10^9/L.
2. The patient has adequate renal function as defined by a serum creatinine ≤1.5
times the ULN, or creatinine clearance (measured via 24-hour urine collection)
≥50 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour
urine collection to calculate creatinine clearance must be performed).
3. The patient has adequate hepatic function as defined by a total bilirubin ≤1.5
mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase
(ALT) ≤ 2.5 times the upper limit of normal (ULN; or 5.0 times the ULN in the
setting of liver metastases).
4. The patient must have adequate coagulation function as defined by international
normalized ratio (INR) ≤1.5
- Within 7 days before the first administration, women of childbearing age must
confirm that the serum pregnancy test is negative and agree to use effective
contraceptives during the study period and within 180 days after the last
administration. In this program, women of childbearing age are defined as sexually
mature women:
1. No hysterectomy or bilateral ovariectomy
2. Natural menopause does not last for 24 months (amenorrhea after cancer
treatment does not rule out fertility) (that is, menstruation occurs at any
time in the previous 24 months).
For male patients whose sexual partners are women of childbearing age, they must agree to
use effective contraception during the study drug use and within 180 days after the last
administration.
Exclusion Criteria:
- Palliative local treatment was given to non-target lesions within 2 weeks before the
first administration, and systemic non-specific immunomodulatory therapy (such as
interleukin, interferon, thymosin, etc.) was received within 2 weeks before the
first administration. Chinese herbal medicine or proprietary Chinese medicine with
anti-tumor indications was received within 2 weeks before the first administration.
- The patient has previously received immune checkpoint inhibitors (such as anti-PD-1
antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint
agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.),
immune cell therapy, etc. any treatment aimed at the immune mechanism of tumor.
- There was a history of gastrointestinal perforation and gastrointestinal fistula
within 6 months before the first administration. If the perforation or fistula has
been removed or repaired, and the disease has been judged by the researchers to
recover or remission, it may be allowed to join the group.
- Active or previously recorded inflammatory bowel disease (such as Crohn's disease or
ulcerative colitis). Unable to swallow, malabsorption syndrome, or uncontrollable
nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect
drug use and absorption.
- There were active malignant tumors in the past 3 years, except for tumors that
participated in the study and local tumors that had been cured. such as skin basal
cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical
carcinoma in situ, breast cancer in situ, localized prostate cancer and so on.
- Active or untreated brain metastases, meningeal metastases, spinal cord compression
or leptomeningeal diseases are known.
However, the patients who met the following requirements and had measurable lesions
outside the central nervous system were allowed to enter the group: asymptomatic after
treatment, imaging was stable for at least 4 weeks before the start of treatment (such as
no new or enlarged brain metastases). And systemic corticosteroids and anticonvulsant
drugs have been stopped for at least 2 weeks.
- There are pleural effusion with clinical symptoms, pericardial effusion or ascites
requiring frequent drainage (≥ 1 / month).
- Study active autoimmune diseases that require systematic treatment within 2 years
before the start of treatment, or researchers determine the existence of autoimmune
diseases that may recur or plan treatment. Except for the following:
1. Skin diseases that do not require systematic treatment (e.g. vitiligo, hair
loss, psoriasis or eczema)
2. Hypothyroidism caused by autoimmune thyroiditis requires only a stable dose of
hormone replacement therapy.
3. Type I diabetes mellitus requiring only a stable dose of insulin replacement
therapy
4. Asthma has been completely relieved in childhood and no intervention is needed
in adults.
5. The researchers determined that the disease would not recur without external
triggers.
- There are any of the following cardio-cerebrovascular diseases or
cardio-cerebrovascular risk factors:
1. Within 6 months before the first administration, there were myocardial
infarction, unstable angina pectoris, cerebrovascular accident, transient
ischemic attack, acute or persistent myocardial ischemia, symptomatic heart
failure (according to New York Heart Association functional grade 2 or above),
symptomatic or poorly controlled arrhythmia, or any arterial thromboembolic
event.
2. There was a history of deep venous thrombosis, pulmonary embolism or other
severe thromboembolism within 3 months before the first administration.
3. There are major vascular diseases, such as aortic aneurysm, aortic dissecting
aneurysm, internal carotid artery stenosis, which may be life-threatening or
require surgery within 6 months.
4. Previous history of myocarditis and cardiomyopathy.
5. Left ventricular ejection fraction (LVEF) < 50%.
- Toxicity that has not been alleviated by previous antineoplastic therapy is defined
as undiminished to Grade 0 or 1 of the National Cancer Institute (NCI) General
terminology Standard for adverse events (CTCAE) (NCICTCAEv5.0), or to the level
specified in the selection / exclusion criteria, with the exception of alopecia /
pigmentation. The patients who develop irreversible toxicity and are not expected to
increase after drug administration (such as hearing loss) may be included in the
study after consultation with researchers. Long-term toxicity caused by radiotherapy
may be included in the study after consultation with the researchers who are
determined by the researchers to be unable to recover.
- Grade 2 peripheral nerve disease was defined according to NCI CTCAE v5.0 standard.
- Interstitial lung disease or non-infectious pneumonia is known to be symptomatic or
requires systemic glucocorticoid treatment in the past, and researchers have
determined that it may affect toxicity assessment or management associated with
research treatment.
- Active tuberculosis is known to exist. The patients suspected of having active
pulmonary tuberculosis should be examined for chest X-ray, sputum and excluded by
clinical symptoms and signs.
- Received systemic anti-infective therapy (excluding antiviral therapy for hepatitis
B or C) within 2 weeks before the first administration.
- The history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation are known.
- There are clinical active hemoptysis, active diverticulitis, abdominal abscess and
gastrointestinal obstruction.
- There were significant clinical bleeding symptoms or definite bleeding tendency
within 1 month before the first administration, such as gastrointestinal bleeding,
hemorrhagic gastric ulcer, or vasculitis.
- It is known that endoscopy shows signs of active bleeding.
- There were other major operations in addition to the diagnosis of gastric cancer
within 28 days before the first administration.
- Untreated active hepatitis B patients (HBsAg positive and HBV-DNA more than 1000
copies / ml [200IU/ml] or higher than the detection lower limit), patients with
hepatitis B were required to receive anti-HBV treatment during the study treatment;
active hepatitis C patients (HCV antibody positive and HCV-RNA levels higher than
the detection lower limit).
- Those who are known to have a history of immunodeficiency or are HIV positive.
- Known active syphilis infection.
- Is participating in another clinical study, unless it is a follow-up period for
observational, non-interventional clinical studies or interventional studies.
- The patients who needed systemic treatment with glucocorticoids (> 10mg/ prednisone
or equivalent dose) or other immunosuppressive drugs within 14 days before the first
administration. Except for the following:
1. If there is no active autoimmune disease, inhaled, ophthalmic or topical
glucocorticoids or doses of ≤ 10mg/ prednisone or equivalent doses of other
glucocorticoids are allowed.
2. Physiological dose of systemic glucocorticoid ≤ 10mg/ prednisone or equivalent
dose of other glucocorticoids.
3. Glucocorticoids are used as pretreatment of infusion-related reactions or
allergic reactions (such as medication before CT examination).
- The live vaccine was given within 30 days of the first administration, or is planned
during the study period.
- A history of severe hypersensitivity to other monoclonal antibodies is known.
- It is known to be unable to meet the requirements of the trial because of mental
illness or substance abuse disorder.
- The patients who are known to have a history of allergy or hypersensitivity to drugs
or any of its components in the combined immunotherapy regimen.
- The patient is pregnant or breastfeeding.
- The researchers believe that there may be a risk of receiving the study drug
treatment, or any condition that will interfere with the evaluation of the study
drug or the safety of the patients or the interpretation of the research results.
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Army Medical Center
Address:
City:
Chongqing
Zip:
400000
Country:
China
Status:
Recruiting
Contact:
Last name:
wang bin
Email:
wb_tmmu@126.com
Contact backup:
Last name:
wang lei
Email:
wlei_amu@163.com
Start date:
September 1, 2022
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Agency class:
Other
Source:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05515796
