PD-1 Antibody Combined With Apatinib Mesylate as 2+ Line Treatment of Serum AFP-elevated Gastric Adenocarcinoma: an Open-label, Single-arm, Multicenter Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- PD-1 antibody
- Conditions
- Gastric Cancer
- Sponsor
- China Medical University, China
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of PD-1 antibody combined with apatinib mesylate in patients with unresectable, local advanced recurrent or metastatic serum AFP-elevated gastric adenocarcinoma, who have at least received first-line antitumor therapy or whose standard treatment is intolerable.
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 prognosis. This prospective study is a single-arm, open-label, multi-center phase II clinical trial to evaluate the efficacy and safety of PD-1 antibody combined with apatinib mesylate in patients with unresectable, local advanced recurrent or metastatic serum AFP-elevated gastric adenocarcinoma, who have at least received first-line antitumor therapy or whose standard treatment is intolerable. 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. PD-1 antibody combined with apatinib mesylate will be administered. PD-L1 expression and TMB will be measured before treatment. In addition, the dynamic changes of serum AFP levels, T lymphocyte in peripheral blood will be monitored before each treatment cycle. 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 cancer, and have histologically confirmed predominant adenocarcinoma with serum AFP-elevated (serum AFP \> 20 ng/ml).
- •Subject must have at least received first-line antitumor therapy or whose standard treatment is intolerable.
- •Subject must have at least one measurable lesion or evaluable disease by CT or MRI per iRECIST 1.1 criteria.
- •Subject must be previously untreated with anti-angiogenesis molecular targeted therapy and immunotherapy for gastric cancer (including anti-CTLA-4, PD-1/PD-L1 monoclonal antibody immunotherapy).
- •ECOG performance status score of 0 or
- •Child-Pugh score \< 6 (Child-Pugh A), and no history of hepatic encephalopathy.
- •Expected survival: ≥12 weeks.
- •Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
Exclusion Criteria
- •With history of active autoimmune disease or autoimmune disease (For example, the following, 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:
- •Controlled Type I diabetes
- •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 ≤ 14 days before randomization.
- •A history of severe allergy to any monoclonal antibody or anti-angiogenesis targeted drug.
- •Patients with known central nervous system metastasis (suspected need to be excluded by MRI scans) or a history of hepatic encephalopathy.
- •The total volume of liver metastases\>50%, or obvious infiltration of bile duct or portal vein trunk, or patients who have received liver transplantation in the past.
- •More than a small amount of pericardial effusion, uncontrollable pleural effusion or ascites requiring frequent drainage or medical intervention.
- •Uncontrollable hypertension with drugs (systolic pressure ≥140 mmHg or diastolic pressure≥90 mmHg).
- •With history of serious cardiovascular and cerebrovascular diseases:
Arms & Interventions
PD-1 antibody + Apatinib mesylate
Every patient will receive PD-1 antibody 200mg iv every 2 weeks and apatinib 250mg or 500mg (according to the patient's tolerance) orally every day. PD-1 antibody will be administered until disease progression or lasts for two years. Apatinib mesylate will be administered until disease progression.
Intervention: PD-1 antibody
PD-1 antibody + Apatinib mesylate
Every patient will receive PD-1 antibody 200mg iv every 2 weeks and apatinib 250mg or 500mg (according to the patient's tolerance) orally every day. PD-1 antibody will be administered until disease progression or lasts for two years. Apatinib mesylate will be administered until disease progression.
Intervention: Apatinib mesylate
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 iRECIST v1.1
Secondary Outcomes
- 6-month/9-month/12-month survival rate(6-month/9-month/12-month)
- Duration of response (DOR)(2 years)
- Progression-free survival (PFS)(2 years)
- Overall survival (OS)(2 years)
- Disease control rate (DCR)(2 years)
- Incidence of Treatment-Emergent Adverse Events(2 years)
- Quality of life (QLQ C30)(Every 2 weeks after the first treatment until 2 years)
- Exploration of biomarkers(2 years)