Overview

XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma

Status:
Not yet recruiting
Trial end date:
2027-02-01
Target enrollment:
0
Participant gender:
All
Summary
This is an open label, randomized, phase Ⅱ, multi-cohort study to treat subjects with ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma. The patients will be randomized into two arms consist of Penpulimab + Anlotinib (3 weeks/cycle) + XELOX and XELOX at a ratio of 1:1. This study is conducted to assess safety and anti-tumor activity of the monoclonal antibody Penpulimab in combination with Anlotinib and standard chemotherapy as adjuvant treatment for ctDNA-positive Gastric, or Gastroesophageal Junction Carcinoma.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
The First Affiliated Hospital with Nanjing Medical University
Collaborator:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Treatments:
Capecitabine
Oxaliplatin
Criteria
Inclusion Criteria:

- Subjects aged ≥18 and ≤75 years old, male or female.

- ECOG performance status score 0-1.

- Histologically or cytologically confirmed GC or GEJ carcinoma, had been treated with
Radical resection (D2, R0 or R1) of gastric cancer.

- Pathological stage:II-III (8th AJCC TNM).

- Estimated lifetime is greater than 6 months.

- The main organs are functioning well, and the blood test results within 14 days before
enrollment should meet the following requirements:

1. Routine blood test:

1. Hemoglobin (HB) ≥90 g/L.

2. Neutrophil count (ANC) ≥1.5×109/L.

3. Platelet count (PLT) ≥100×109/L.

2. Biochemical test:

1. Total bilirubin≤1.5×ULN (upper limit of normal).

2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤
2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN.

3. Serum creatinine (Cr) ≤1.5 ULN or creatinine clearance ≥60mL/min.

- No obvious clinical symptoms of heart disease.

- Must have disease-free status documented by complete physical examination and imaging
studies with no evidence of recurrent, residual, or metastatic disease on standard
imaging (chest, abdomen, and pelvis captured by CT chest and CT or MRI of abdomen and
pelvis) per investigator assessment within 28 days prior to enrollment.

- Females of childbearing potential must have a negative urine or serum pregnancy test
within 7 days of randomization and must be willing to use a highly effective method of
birth control (Appendix 9) for the duration of the study, and ≥ 120 days after the
last dose of penpulimab and 180 days after the last dose of chemotherapy.

- Volunteer to participate in this study and sign an informed consent form.

Exclusion Criteria:

- Participation in other drug clinical trials within four weeks.

- Multiple factors affecting oral medication (such as inability to swallow, chronic
diarrhea and intestinal obstruction.

- History of bleeding, any bleeding event with a severity grade of 3 or higher per CTCAE
5.0 within 4 weeks before screening.

- Patients with known central nervous system metastasis or history of central nervous
system metastasis prior to screening. For patients with clinically suspected central
nervous system metastases, CT or MRI must be performed within 28 days before
enrollment to rule out central nervous system metastases.

- Patients with hypertension and uncontrolled by antihypertensive drugs alone (systolic
blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); Patients with a
history of unstable angina pectoris; Patients newly diagnosed as angina pectoris
within 3 months before screening or myocardial infarction events within 6 months
before screening; Arrhythmias (including QTcF ≥ 450 ms in men, ≥ 470 ms in women
requiring long-term use of antiarrhythmic drugs and New York Heart Association Class ≥
II cardiac insufficiency;There are many factors that affect oral drug absorption (such
as inability to swallow, nausea and vomiting, upper gastrointestinal obstruction,
abnormal physiological function, malabsorption syndrome, etc.), which may affect
anlotinib hydrochloride absorbers.

- Long-term unhealed wound or unhealed fracture.

- Imaging findings show that the tumor has invaded around important blood vessels or the
patient's tumor has a very high possibility of invading important blood vessels during
treatment and causing fatal massive hemorrhage as judged by the investigator.

- Patients with abnormal coagulation function and bleeding tendency (the following
criteria must be met within 14 days before randomization: INR is within normal range
without anticoagulants or has no clinically significant abnormality); patients treated
with anticoagulants or vitamin K antagonists such as warfarin, heparin or their
analogues; patients with prothrombin time international normalized ratio (INR) ≤ 1.5
are allowed to take low-dose warfarin (1 mg orally, once daily) or low-dose aspirin
(the daily dose does not exceed 100 mg) for preventive purposes.

- Arteriovenous thrombotic events occurred within 6 months before screening, such as
cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis
(except venous thrombosis caused by previous chemotherapy that has been judged by the
investigator to have recovered) and pulmonary embolism.

- Urine routine showed urine protein and 24 h urine protein was confirmed to be > 1.0g.

- Previous use of immune targeted therapy drugs.

- History of immunodeficiency, or other acquired or congenital immunodeficiency
diseases, or history of organ transplantation.

- Patients with infectious pneumonia, pneumonitis, interstitial pneumonia and other
conditions requiring corticosteroids.

- History of severe chronic autoimmune diseases, such as systemic lupus erythematosus;
history of inflammatory bowel disease such as ulcerative enteritis, Crohn's disease,
irritable bowel syndrome and other chronic diarrheal diseases; history of sarcoidosis
or tuberculosis; history of active hepatitis B, C and HIV infection; well-controlled
non-serious immune diseases, such as dermatitis, arthritis, psoriasis, etc. Hepatitis
B virus < 1000 copies/ml can be detected.

- Patients with hypersensitivity to human or murine monoclonal antibodies.

- Patients with a history of psychotropic substance abuse and unable to quit or with
mental disorders.

- Pleural or peritoneal effusion with clinical symptoms requiring clinical intervention.

- Patients who do not follow the doctor's advice, do not take medicine as required, or
have insufficient data that can affect the efficacy judgment or safety judgment.

- Patients with concomitant diseases that, in the judgment of the investigator,
seriously jeopardize the patient's safety or affect the patient's completion of the
study.