Trial Title:
Concurrent Chemoradiotherapy Combined With Sintilimab as Neoadjuvant Therapy for GC Patients With PALM
NCT ID:
NCT06341595
Condition:
Gastric Cancer
Gastric Cancer Metastatic to Regional Lymph Nodes
Conditions: Official terms:
Stomach Neoplasms
Oxaliplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
Sintilimab: 200mg iv q3w d1, 4-6 cycles
Arm group label:
combination therapy
Intervention type:
Radiation
Intervention name:
Extraperitoneal radiation therapy
Description:
Radiotherapy using extraperitoneal radiation therapy, once a day, 5 times a week, 1.8-2
Gy/f, a total of 45-50.4 Gy (lymph node lesion radiation dose of 60-66 Gy)
Arm group label:
combination therapy
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
oxaliplatin: 130mg/m^2, D1, Q3W, 4-6 cycles
Arm group label:
combination therapy
Intervention type:
Drug
Intervention name:
S-1
Description:
S-1: 40mg/m^2, bid, d1-14, 4-6 cycles
Arm group label:
combination therapy
Summary:
This trial is a prospective, single arm, single center, phase II clinical study aimed at
subjects with advanced gastric cancer and para aortic lymph node metastasis, exploring
the feasibility and safety of Sintilimab Injection combined with synchronous
chemo-radiotherapy as neoadjuvant therapy.
Patients will receive sintilimab Injection (200mg iv q3w d1) combined with concurrent
radiotherapy and chemotherapy. The chemotherapy regimen will use oxaliplatin 130mg/m2+S-1
40mg/m2 bid d1-14. Radiotherapy is performed using intraperitoneal radiation therapy,
once a day, five times a week, at a dose of 1.8-2 Gy/f, for a total of 45-50.4 Gy (60-66
Gy for lymph node lesions). Radiation therapy starts from the second cycle of Sintilimab
Injection combined with chemotherapy. The subjects underwent imaging evaluation after
completing 4 cycles of combination chemotherapy and radiation therapy with Sintilimab
Injection. Evaluated as a surgical subject (surgical conditions: imaging evaluation of
enlarged lymph nodes adjacent to the abdominal aorta with PR or no significant activity),
radical surgery will be performed within 4 weeks after the last study drug treatment.
After surgery, the researcher will determine the necessity of adjuvant treatment and
develop an adjuvant treatment plan based on the subject's condition. Subjects evaluated
as inoperable will have their best follow-up treatment plan determined by the researcher.
Criteria for eligibility:
Criteria:
Inclusion criteria:
- Able to provide informed consent and willing to sign an approved consent form;
- age ≥ 18 years old and ≤ 75 years old, male and female;
- Has histologically confirmed diagnosis of gastric or GEJ adenocarcinoma;
- patients with advanced gastric cancer who have para aortic lymph node metastasis at
the initial treatment and whose primary tumor site can be treated with D2 radical
operation;
- peritoneal exploration to exclude peritoneal metastasis, liver metastasis and other
metastasis;
- CT or MRI, PET-CT and other examinations suggest that there is only one unresectable
factor, namely, para aortic lymph node metastasis;
- has not receive previous anti-tumor treatment (radiotherapy, chemotherapy, targeted
or immunotherapy, etc.);
- Has at least one measurable lesion as defined by RECIST 1.1 as determined by
investigator assessment.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- expected survival time >3 months;
- sufficient organ function, the subject needs to meet the following laboratory
indicators:
1. The absolute neutrophil count (ANC) ≥ 1.5x109/l without granulocyte colony
stimulating factor in the past 14 days.
2. Platelets ≥ 100 without blood transfusion in recent 14 days × 109/l.
3. Hemoglobin >9g/dl without blood transfusion or use of erythropoietin in recent
14 days;
4. Total bilirubin ≤ 1.5 × Upper limit of normal value (ULN);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were ≤ 2.5
× ULN (ALT or AST ≤ 5 allowed for subjects with liver metastasis × ULN);
6. Blood creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by Cockcroft
Gault formula) ≥ 60 ml/min;
7. Good coagulation function, defined as international normalized ratio (INR) or
prothrombin time (PT) ≤ 1.5 times ULN;
8. Thyroid function was normal, defined as thyroid stimulating hormone (TSH)
within the normal range. If baseline TSH is outside the normal range, subjects
with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
- Women of childbearing potential (WOCBP) must have a negative urine or serum
pregnancy test at the timing of enrollment. Women of non-childbearing potential was
defined as having a cessation of menses for one or more year or having surgical
sterilization/Hysterectomy
- Participants of childbearing potential must be willing to use an adequate method of
contraception （method with failure rate less than 1% in a year）for the course of the
study through 120 days after the last dose of study medication or through 180 days
of last dose of chemotherapy.
Exclusion criteria:
- HER-2 positive status
- peritoneal or other organ metastasis;
- endoscopy shows signs of active bleeding, and history of gastrointestinal
perforation and /or fistula within 6 months before enrollment.;
- other malignant diseases other than gastric cancer diagnosed within 5 years before
the first administration (excluding skin basal cell carcinoma, skin squamous
epithelial carcinoma, and / or carcinoma in situ after radical resection);
- Is currently participating in and receiving study therapy , or having been treated
with another research drug or with an investigational medical devices within 4 weeks
before the first administration;
- Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, anti-PD
L2 , anti-CD137,anti-CTLA-4 agent or with an agent directed to another stimulatory
or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137);
- have received systemic treatment with Chinese patent drugs with anti-tumor
indications or drugs with immunomodulatory effects (including thymosin, interferon,
interleukin, except for local use to control ascites) within 2 weeks before the
first administration;
- active autoimmune disease requiring systemic treatment (such as the use of disease
modifying drugs, glucocorticoids or immunosuppressants) occurred within 2 years
before the first administration. Alternative therapies (such as thyroxine, insulin,
or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are
not considered systemic treatments;
- being treated with systemic glucocorticoids (excluding nasal spray, inhalation or
other local glucocorticoids) or any other form of immunosuppressive therapy within 7
days before the first dose of the study;
Note: physiological doses of glucocorticoids (≤ 10 mg/ day of prednisone or equivalent)
are allowed;
- Known history of allogeneic organ (except corneal transplantation) or allogeneic
hemopoietic stem cell transplantation;
- Known allergy or hypersensitivity to the investigational drugs Sintilimab,
Oxaliplatin, S-1 or excipients;
- there are many factors that affect oral drugs (such as inability to swallow, after
gastrointestinal resection, chronic diarrhea and intestinal obstruction, cardiac and
pyloric obstruction affecting eating and gastric emptying);
- have not fully recovered from the toxicity and / or complications caused by any
intervention before starting treatment (i.e., ≤ grade 1 or reaching baseline,
excluding fatigue or hair loss);
- Human Immunodeficiency Virus (HIV) infection (HIV antibody positive) (i.e. HIV 1/2
antibody positive);
- uncontrolled active hepatitis B (defined as HBsAg positive with HBV-DNA copy number
greater than the upper limit of normal value in the laboratory of the research
center);
Note: hepatitis B subjects who meet the following criteria can also be enrolled:
1. HBV viral load was <1000 copies /ml (200 iu/ml) before the first dose, and subjects
should receive anti HBV treatment throughout the study drug treatment period to
avoid virus reactivation
2. For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-),
prophylactic anti HBV treatment is not required, but viral reactivation needs to be
closely monitored
- active HCV infected subjects (HCV antibody positive and HCV-RNA level higher
than the lower limit of detection);
- vaccinated with live vaccine within 30 days before the first administration
(cycle 1, day 1);
Note: it is allowed to receive inactivated virus vaccine for injection against seasonal
influenza within 30 days before the first administration; However, live attenuated
influenza vaccines administered intranasally are not allowed.
- Women who are pregnant or nursing.
- there are any serious or uncontrollable systemic diseases, such as:
1. The resting ECG has major abnormalities in rhythm, conduction or morphology,
and the symptoms are serious and difficult to control, such as complete left
bundle branch block, heart block above grade II, ventricular arrhythmia or
atrial fibrillation;
2. Unstable angina, congestive heart failure, chronic heart failure with New York
Heart Association (NYHA) classification ≥ 2;
3. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction,
unstable angina pectoris, cerebrovascular accident or transient ischemic
attack, occurred within 6 months before enrollment;
4. Blood pressure control was not ideal (systolic blood pressure > 140 mmHg,
diastolic blood pressure > 90 mmHg);
5. There was a history of non infectious pneumonia requiring glucocorticoid
treatment within 1 year before the first administration, or there was currently
clinically active interstitial lung disease;
6. Active pulmonary tuberculosis;
7. The presence of active or uncontrolled infections requiring systemic treatment;
8. There were clinically active diverticulitis, abdominal abscess,
gastrointestinal obstruction;
9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic
active hepatitis;
10. Poor control of diabetes (fasting blood glucose (FBG) > 10mmol/l);
11. The urine routine showed that the urine protein was ≥ + +, and the 24-hour
urine protein quantitation was confirmed to be > 1.0 G;
12. Those who have mental disorders and cannot cooperate with treatment;
- Other acute or chronic diseases, mental illness, or abnormal laboratory test results
that may lead to the following outcomes: increase the risk of participating in study
or study drug administration, or interfere with the interpretation of the study
results and considered by investigator as "NOT" eligible to participate in this
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Jiangsu Province Hospital
Address:
City:
Nanjing
Zip:
210029
Country:
China
Status:
Recruiting
Contact:
Last name:
Yang Yan
Start date:
April 1, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06341595
