Anti-PD-1 Antibody Combined With Chemotherapy as First-line Treatment of Serum AFP-elevated Gastric or Gastroesophageal Junction Adenocarcinoma: a Single-arm, Multicenter Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- Anti-PD-1 antibody
- Conditions
- Gastric or Gastroesophageal Junction Adenocarcinoma
- Sponsor
- China Medical University, China
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of of anti-PD-1 antibody in combination with chemotherapy as first-line treatment in patients with unresectable, locally advanced recurrent or metastatic serum AFP-elevated gastric and gastroesophageal junction adenocarcinoma.
Detailed Description
AFP-elevated gastric adenocarcinoma is a special type of gastric cancer, with the characteristics of high risk of liver and lymph node metastasis, poor therapeutic effect, and dismal prognosis. This prospective study is a single-arm, multicenter phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody in combination with chemotherapy as first-line treatment in patients with unresectable, locally advanced recurrent or metastatic serum AFP-elevated gastric and gastroesophageal junction adenocarcinoma. AFP elevation is defined as serum AFP \> 20 ng/ml. In this prospective study, the objective remission rate (ORR) will be used as primary outcome measures and 30 patients will be recruited. Anti-PD-1 antibody in combination with chemotherapy will be administered. PD-L1 expression and tumor mutant burden (TMB) will be measured before treatment. In addition, the dynamic changes of serum AFP levels, T lymphocyte in peripheral blood will be monitored during treatment. In the course of treatment, safety evaluation will be carried out according to the standard of adverse reaction classification (CTCAE) 4.0.
Investigators
Jingdong Zhang
Director
China Medical University, China
Eligibility Criteria
Inclusion Criteria
- •Patients must volunteer to participate in the study, signed informed consent, and were able to comply with the program requirements of visits and related procedures.
- •Age and gender: ≥18 years old and≤75 years old, both men and women.
- •All subjects must have unresectable, local advanced recurrent or metastatic gastric adenocarcinoma (GC) or gastroesophageal junction adenocarcinoma (GEC) confirmed by histologically.
- •No systematic treatment for advanced or metastatic GC/GEC has been received in the past. For patients who have received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy and/or radiochemotherapy) for GC/GEC in the past, the last treatment must be completed at least six months before the start of study drug. Subjects are allowed to receive palliative radiotherapy, but it must be completed two weeks before the start of study drug.
- •Serum AFP \> 20 ng/ml.
- •All acute toxic reactions caused by previous medication or surgery were alleviated to grade 0-1 (according to NCI-CTCAE version 5.0) or to the level specified by the criteria for Inclusion/exclusion. The toxicities that do not pose a safety risk to patients determined by investigators are excluded, such as hair loss , etc.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Expected survival: ≥12 weeks.
- •Subject must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST 1.1 criteria.
- •The functions of important organs must meet the following requirements:(1)Hematological system: Neutrophil count≥1.5×10\^9/L; Platelet count≥80×10\^9/L; Hemoglobin≥90g/L;(2)Liver function: Serum albumin≥28g/L; Total bilirubin (TBI)≤1.5×ULN; Alanine aminotransferase (ALT)≤2.5×ULN (or≤5×ULN if liver metastases are present); Aspartate aminotransferase (AST)≤2.5×ULN (or≤5×ULN if liver metastases are present); (3)Renal function: Serum creatinine≤1.5×ULN or calculated creatinine clearance (CrCl) ≥40 mL/min (using the Cockcroft-Gault formula):Female CrCl = (140- age in years) × weight in kg × 0.85/ 72 × serum creatinine in mg/ dL; Male CrCl = (140- age in years) × weight in kg × 1.00/72 × serum creatinine in mg/ dL;(4)Coagulation function: Subjects not receiving anticoagulation therapy: (International Normalized Ratio) INR or activeated partial thromboplastin time (APTT) ≤ 1.5×ULN.
Exclusion Criteria
- •Known human epidermalgrowth factor receptor-2 (HER2) positive.
- •Currently participating in research and receiving research treatment, or participating in the research of experimental drugs within four weeks before the start of study drug, and having received research treatment or used experimental instruments.
- •Major surgery were performed within 4 weeks before the start of the study and incomplete recovery.
- •Existence of any active autoimmune disease or with a history of autoimmune disease (as the following examples, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary, vasculitis, nephritis, hyperthyroidism; patients with vitiligo; in childhood asthma has been completely alleviated, adults without any intervention can be included; asthma with medical intervention could not be included). Substitution therapy is not considered as systemic therapy. Patients with the following diseases are not excluded and may proceed to further screening: a. Controlled Type I diabetes; b. Hypothyroidism (provided it is managed with hormone replacement therapy only).
- •Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 7 days before randomization.
- •Any active malignancy ≤ 5 years before randomization except for the specific cancer under investigation in this study and any cured limited tumors (eg, carcinoma in situ of the cervix or prostate, basal cell skin cancer).
- •Patients with known central nervous system metastasis (suspected need to be excluded by MRI scans) or a history of hepatic encephalopathy.
- •A history of pneumonia (non-infectious) requiring steroid therapy within 6 months or currently suffering from pneumonia (pulmonary infectious).
- •With active infections, fever of unknown origin (≥38.5℃) within 7 days before the start of study drug; or white blood cell count at baseline \> 15×10\^9/L); with severe chronic or active infections (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy during screening period, excluding viral hepatitis.
- •With any other disease, metabolic abnormality, abnormal physical examination or abnormal laboratory examination, according to the judgments of the investigators, there is reason to suspect that the patient has a certain disease or condition that is not suitable for the use of study drugs, or that it will affect the interpretation of research results or put the patient at high risk.
Arms & Interventions
Experimental: Anti-PD-1 antibody＋XELOX
Every patient will receive anti-PD-1 antibody (200 mg intravenous drip every 3 weeks) and XELOX regimen chemotherapy (Oxaliplatin 130 mg/m2, intravenous drip, d1; Capecitabine 1000mg/ kg, twice a day, orally, d1-14;every 21 days). Anti-PD-1 antibody will be administered until the disease progresses or lasts for two years. XELOX will be administered 6-8cycles，followed by capecitabine monotherapy, the course of treatment is determined by the investigators according to clinical practice.
Intervention: Anti-PD-1 antibody
Experimental: Anti-PD-1 antibody＋XELOX
Every patient will receive anti-PD-1 antibody (200 mg intravenous drip every 3 weeks) and XELOX regimen chemotherapy (Oxaliplatin 130 mg/m2, intravenous drip, d1; Capecitabine 1000mg/ kg, twice a day, orally, d1-14;every 21 days). Anti-PD-1 antibody will be administered until the disease progresses or lasts for two years. XELOX will be administered 6-8cycles，followed by capecitabine monotherapy, the course of treatment is determined by the investigators according to clinical practice.
Intervention: XELOX
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: 2 years
The proportion of patients whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by RECIST v1.1.
Secondary Outcomes
- Duration of response (DOR)(2 years)
- 6-month/9-month/12-month survival rate(6-month/9-month/12-month)
- Progression-free survival (PFS)(2 years)
- Overall survival (OS)(2 years)
- Disease control rate (DCR)(2 years)
- Quality of life score (QLQ-C30)(Every 2 weeks after the first treatment until 2 years)
- Incidence of Treatment-Emergent Adverse Events(2 years)
- Exploration of biomarkers (PD-L1 expression, TMB at the baseline, changes of AFP and T lymphocyte in peripheral blood)(2 years)