Trial Title:
XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma
NCT ID:
NCT05494060
Condition:
Carcinoma
Gastrointestinal Diseases
Stomach Cancer
Gastroesophageal-junction Cancer
Digestive System Diseases
Gastric Cancer
Gastrointestinal Neoplasms
Conditions: Official terms:
Adenocarcinoma
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Capecitabine
Oxaliplatin
Conditions: Keywords:
Penpulimab
Anlotinib
Capecitabine
Oxaliplatin
ctDNA
adjuvant therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Experimental: Penpulimab + Anlotinib + XELOX; Active Comparator: XELOX
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Anlotinib hydrochloride capsule
Description:
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in
21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21);
Arm group label:
Penpulimab + Anlotinib + XELOX
Intervention type:
Drug
Intervention name:
Penpulimab Injection
Description:
Penpulimab Injection 100mg per bottle, 200mg IV Day 1, cycled every 21 days
Arm group label:
Penpulimab + Anlotinib + XELOX
Other name:
AK-105
Intervention type:
Drug
Intervention name:
XELOX
Description:
Capecitabine:1000 mg/m2 bid d1-14 q3w, Oxaliplatin:130 mg/m2 d1 q3w
Arm group label:
Penpulimab + Anlotinib + XELOX
Arm group label:
XELOX
Other name:
Capecitabine and Oxaliplatin
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.
Detailed description:
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. The study includes a screening (up to 28 days), treatment (disease
recurrence, unacceptable toxicity, or subject withdrawal of consent with a maximum 12
month), safety follow-up (up to 30 days following last study drug treatment), and
survival follow-up phase.
Criteria for eligibility:
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: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.
- Considering that NGS analysis may take up to 10 working days, patients could receive
1 cycle of XELOX chemotherapy after ctDNA sampling.
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.
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:
Yongqian Shu, PhD
Phone:
00862568306428
Email:
shuyongqian@csco.org.cn
Contact backup:
Last name:
Xiaofeng Chen, PhD
Phone:
008613585172006
Email:
xiaofengch198019@126.com
Start date:
March 16, 2022
Completion date:
February 2027
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Collaborator:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
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/NCT05494060