Clinical Trials /

PD-1 Antibody + XELOX in 1st Line Serum A-fetoprotein (AFP)-Elevated Gastric or Gastroesophageal Junction Adenocarcinoma

NCT04098796

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PD-1 Antibody + XELOX in 1st Line Serum A-fetoprotein (AFP)-Elevated Gastric or Gastroesophageal Junction Adenocarcinoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PD-1-CT-Ⅱ-1st L-AFPGC
  • NCT ID: NCT04098796

Conditions

  • Gastric or Gastroesophageal Junction Adenocarcinoma
  • AFP

Interventions

DrugSynonymsArms
Anti-PD-1 antibodyExperimental: Anti-PD-1 antibody+XELOX
XELOXExperimental: Anti-PD-1 antibody+XELOX

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental: Anti-PD-1 antibody+XELOXExperimentalEvery 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.
  • Anti-PD-1 antibody
  • XELOX

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Age and gender: ≥18 years old and≤75 years old, both men and women.

          3. All subjects must have unresectable, local advanced recurrent or metastatic gastric
             adenocarcinoma (GC) or gastroesophageal junction adenocarcinoma (GEC) confirmed by
             histologically.

          4. 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.

          5. Serum AFP > 20 ng/ml.

          6. 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.

          7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

          8. Expected survival: ≥12 weeks.

          9. Subject must have at least one measurable lesion or evaluable disease by CT or MRI per
             RECIST 1.1 criteria.

         10. 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.

         11. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test within 7 days prior to the start of study drug. WOCBP must agree to follow
             instructions for method(s) of contraception (e.g. intrauterine devices,
             contraceptives, condoms or abstinence) for the duration of study treatment and 6
             months after the last dose of study treatment. Subjects must be non-lactating. Males
             who are sexually active with WOCBP must agree to follow instructions for method(s) of
             contraception for the duration of study treatment and 6 months after the last dose of
             study treatment.

        Exclusion Criteria:

          1. Known human epidermalgrowth factor receptor-2 (HER2) positive.

          2. 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.

          3. Major surgery were performed within 4 weeks before the start of the study and
             incomplete recovery.

          4. 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).

          5. Any condition that required systemic treatment with either corticosteroids (> 10 mg
             daily of prednisone or equivalent) or other immunosuppressive medication ≤ 7 days
             before randomization.

          6. 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).

          7. Patients with known central nervous system metastasis (suspected need to be excluded
             by MRI scans) or a history of hepatic encephalopathy.

          8. A history of pneumonia (non-infectious) requiring steroid therapy within 6 months or
             currently suffering from pneumonia (pulmonary infectious).

          9. 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.

         10. 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.

         11. Mental or drug abuse disorders known to have an impact on compliance with study
             requirements

         12. Congenital or acquired immunodeficiency (e.g. HIV-infected persons).

         13. With active hepatitis B virus (HBV) or hepatitis C virus (HCV). Active hepatitis B is
             defined as known positive HBsAg results, and HBV-DNA > 2000IU/ml. Active hepatitis C
             is defined as known positive hepatitis C antibodies and the quantitative results of
             HCV RNA are higher than the lower detection limit of analytical methods. Active HBV
             will be allowed if they have HBV DNA < 500 IU/mL (or 2500 copies/mL) at screening.
             Patients with HBV-DNA < 2000IU/ml through antiviral therapy can be considered
             included.

         14. Was administered a live attenuated vaccine ≤ 4 weeks before randomization, or plan to
             vaccinate during treatment with against PD-1 monoclonal antibody or within five months
             after last administration.

         15. More than a small amount of pericardial effusion, uncontrolled pleural effusion or
             clinically obvious peritoneal effusion at screening. It is defined as meeting the
             following criteria: physical examination at screening can detect pleural and
             peritoneal effusion, or in screening process, pleural and peritoneal effusion needs
             puncture and drainage.

         16. With history of serious cardiovascular and cerebrovascular diseases: (1) Any history
             of heart failure meeting New York Heart Association Classification III or IV or more
             serious history of heart disease, myocardial infarction, or cerebrovascular accident
             in 3 months before randomization;(2) Left ventricular ejection fraction < 50% by color
             Doppler echocardiography;(3) Uncontrollable hypertension; (4) Uncontrolled
             arrhythmias; (5) Acute coronary syndrome, congestive heart failure, stroke,
             thromboembolism or other cardiovascular events above grade 3 within 6 months before
             the start of study drug.

         17. A history of allergy to anti-PD-1, anti-PD-L1 monoclonal antibody drugs or oxaliplatin
             or capecitabine.

         18. Known dihydropyrimidine dehydrogenase deficiency.

         19. Pregnant or lactating women; or female subjects who are expected to conceive during
             the planned trial period (from the start of screening visits to 120 days after the
             last administration of the study) or male subjects whose spouses are pregnant.

         20. Other situations that the researchers think should be excluded.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:The proportion of patients whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by RECIST v1.1.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:The time from the date of randomization to the date of first documentation of disease progression or death, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:The time from the date of randomization until the date of death due to any cause.
Measure:Duration of response (DOR)
Time Frame:2 years
Safety Issue:
Description:The time from CR or PR to disease progression or death.
Measure:Disease control rate (DCR)
Time Frame:2 years
Safety Issue:
Description:The proportion of patients who's BOR is CR, PR, and stable disease (SD) assessed.
Measure:6-month/9-month/12-month survival rate
Time Frame:6-month/9-month/12-month
Safety Issue:
Description:After date of randomization, evaluate patient survival rate at 6,9 and 12 months, respectively.
Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:2 years
Safety Issue:
Description:Incidence of Treatment-Emergent Adverse Events.The grade of toxicity will be assessed using the NCI-CTCAE version 5.0.
Measure:Quality of life score (QLQ-C30)
Time Frame:Every 2 weeks after the first treatment until 2 years
Safety Issue:
Description:Scores according to the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 scoring manual.
Measure:Exploration of biomarkers (PD-L1 expression, TMB at the baseline, changes of AFP and T lymphocyte in peripheral blood)
Time Frame:2 years
Safety Issue:
Description:PD-L1 expression at the baseline using, TMB level at the baseline, changes of serum AFP level and T lymphocyte in peripheral blood at baseline and during the treatment,and etc.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:China Medical University, China

Trial Keywords

  • Gastric or gastroesophageal junction adenocarcinoma
  • AFP
  • PD-1
  • chemotherapy
  • first-line

Last Updated

September 20, 2019