XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma (EXPLORING)
Primary Purpose
Carcinoma, Gastrointestinal Diseases, Stomach Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Anlotinib hydrochloride capsule
Penpulimab Injection
XELOX
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma focused on measuring Penpulimab, Anlotinib, Capecitabine, Oxaliplatin, ctDNA, adjuvant therapy
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: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:
Routine blood test:
- Hemoglobin (HB) ≥90 g/L.
- Neutrophil count (ANC) ≥1.5×109/L.
- Platelet count (PLT) ≥100×109/L.
Biochemical test:
- Total bilirubin≤1.5×ULN (upper limit of normal).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN.
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Penpulimab + Anlotinib + XELOX
XELOX
Arm Description
Penpulimab in combination with Anlotinib and XELOX (Capecitabine and Oxaliplatin)
XELOX (Capecitabine and Oxaliplatin)
Outcomes
Primary Outcome Measures
Disease Free Survival (DFS)
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence).
Secondary Outcome Measures
Disease Free Survival (DFS) rate at 2 years
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence), assessed at 2 years.
Disease Free Survival (DFS) rate at 3 years
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence), assessed at 3 years.
Full Information
NCT ID
NCT05494060
First Posted
August 8, 2022
Last Updated
August 8, 2022
Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05494060
Brief Title
XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma
Acronym
EXPLORING
Official Title
XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma, a Randomized, Controlled, Mulitcenter Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 2022 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
February 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Gastrointestinal Diseases, Stomach Cancer, Gastroesophageal-junction Cancer, Digestive System Diseases, Gastric Cancer, Gastrointestinal Neoplasms
Keywords
Penpulimab, Anlotinib, Capecitabine, Oxaliplatin, ctDNA, adjuvant therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Experimental: Penpulimab + Anlotinib + XELOX; Active Comparator: XELOX
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Penpulimab + Anlotinib + XELOX
Arm Type
Experimental
Arm Description
Penpulimab in combination with Anlotinib and XELOX (Capecitabine and Oxaliplatin)
Arm Title
XELOX
Arm Type
Active Comparator
Arm Description
XELOX (Capecitabine and Oxaliplatin)
Intervention Type
Drug
Intervention Name(s)
Anlotinib hydrochloride capsule
Intervention 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);
Intervention Type
Drug
Intervention Name(s)
Penpulimab Injection
Other Intervention Name(s)
AK-105
Intervention Description
Penpulimab Injection 100mg per bottle, 200mg IV Day 1, cycled every 21 days
Intervention Type
Drug
Intervention Name(s)
XELOX
Other Intervention Name(s)
Capecitabine and Oxaliplatin
Intervention Description
Capecitabine:1000 mg/m2 bid d1-14 q3w, Oxaliplatin:130 mg/m2 d1 q3w
Primary Outcome Measure Information:
Title
Disease Free Survival (DFS)
Description
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence).
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Disease Free Survival (DFS) rate at 2 years
Description
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence), assessed at 2 years.
Time Frame
2 years
Title
Disease Free Survival (DFS) rate at 3 years
Description
From date of receiving therapy until date of disease recurrence or death (by any cause in the absence of recurrence), assessed at 3 years.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Overall survival (OS)
Description
OS defined as the time from the first dose to death from any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up.
Time Frame
up to 4 years
Title
Toxicity by CTCAE v5.0 criteria
Description
oxicity and safety analysis will occur in patients who received at least one full or partial dose of study treatment. Adverse events will be graded per NCI CTCAE v.5.0.
Time Frame
up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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: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:
Routine blood test:
Hemoglobin (HB) ≥90 g/L.
Neutrophil count (ANC) ≥1.5×109/L.
Platelet count (PLT) ≥100×109/L.
Biochemical test:
Total bilirubin≤1.5×ULN (upper limit of normal).
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongqian Shu, PhD
Phone
0086-025-68306428
Email
shuyongqian@csco.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaofeng Chen, PhD
Phone
0086-13585172006
Email
xiaofengch198019@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ext: Shu, PhD
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma
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