Clinical Trials /

Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

NCT04263870

Description:

This study aims to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction
  • Official Title: An Exploratory Study of Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Clinical Trial IDs

  • ORG STUDY ID: BZhang
  • NCT ID: NCT04263870

Conditions

  • Gastroesophageal Junction Adenocarcinoma
  • Stomach Adenocarcinoma
  • Locally Advanced Unresectable Gastric Adenocarcinoma
  • Metastatic Gastric Cancer

Interventions

DrugSynonymsArms
sintilimabcapecitabine, oxaliplatinSintilimab plus capecitabine and oxaliplatin

Purpose

This study aims to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction

Detailed Description

      In a variety of solid tumors such as colorectal cancer, it has been confirmed that some
      selected advanced patients still have a chance to cure through multidisciplinary treatment.
      Because of the poor biological behavior of gastric cancer, few people with advanced gastric
      cancer can benefit from local treatment, and there are fewer related studies. However,
      retrospective and small sample size prospective phase II clinical studies have also shown
      that unresectable locally advanced and some selected limited distant metastatic gastric and
      gastric junction adenocarcinoma patients may also achieve long-term survival through
      multimodal treatment strategies. The triple drug regimens were often used as conversion
      regimens in previous studies. Although the efficiency was improved, the R0 resection rate was
      only about 60%, the disease-free survival was about 10 months, and the toxicity was high. In
      order to improve the survival of these patients, more effective and less toxic treatment
      regimens are urgently needed. Objective response rate was 76.5% with anti-PD-1 antibody
      nivolumab plus CapeOX. The investigators predict that this regimen will achieve good results
      in the conversion treatment of advanced gastric cancer. The investigators intend to carry out
      this study to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion
      therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma
      of the stomach or esophagogastric junction. The primary objectives are 12-month progression-
      free survival (PFS) rate. Secondary objectives include safety, objective response rate (ORR),
      R0 resection rate , tumor regression grading(TRG), progression- free survival (PFS) ,overall
      survival (OS) and exploratory biomarker assessment. Subjects enrolled are treated with oral
      capecitabine 1000mg per m2 bid for two weeks(every 3 weeks)and intravenous oxaliplatin 130mg
      per m2(every 3 weeks)in combination with sintilimab 200mg (every 3 weeks) for 3 cycles. After
      3 cycles of treatment, the tumor was evaluated. The clinical efficacy was evaluated as
      CR\PR\SD. Patients with SD,PR,CR will be treated with surgery. 36 patients will be included
      in this study
    

Trial Arms

NameTypeDescriptionInterventions
Sintilimab plus capecitabine and oxaliplatinExperimentalSubjects enrolled are treated with oral capecitabine 1000mg per m2 bid for two weeks(every 3 weeks)and intravenous oxaliplatin 130mg per m2(every 3 weeks)in combination with sintilimab 200mg (every 3 weeks)
  • sintilimab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologic and/or cytologic diagnosis of unresectable locally advanced or limited
             metastatic adenocarcinoma of the stomach or esophagogastric junction.

          2. Metastatic lesions are resectable or can be controlled by local ablative procedure.

          3. Definition of limited metastatic status:

               1. abdominal, retroperitoneallymphnodemetastases only (eg,para-aortic, intra
                  aortic-caval, peripancreatic, or mesenterial lymph nodes).

               2. One incurable organ site with or without retroperitoneal lymph node metastases.
                  One incurable organ site metastases according to the following schema: -
                  Localized potentially operable peritoneal carcinomatosis or only cytology-
                  positive (Cy1) peritoneal lavage fluid without macroscopic peritoneal metastasis
                  .

                    -  liver metastasis, and the number of liver metastasis ≤ 3 those are
                       potentially resetabl.

                    -  unilateral or bilateral Krukenberg's tumors in the absence of macroscopic
                       peritoneal carcinomatosis.

                    -  unilateral or bilateral adrenal metastases

                    -  Extra-abdominal lymph node metastases such as supraclavicular or cervical
                       lymph node involvement.

          4. Tumor HER-2 is negative.

          5. Age 18-75, gender unlimited.

          6. Survival expectation ≥12 weeks.

          7. Eastern Cooperative Oncology Group (ECOG) 0 or 1.

          8. Not previously treated with any systemic treatment (including HER2 inhibitors), or who
             have metastasis 6 months after the end of adjuvant chemotherapy or neoadjuvant
             chemotherapy. (Note: the use of oxaliplatin in previous adjuvant or neoadjuvant
             therapy should not exceed 800 mg/m2, and the treatment-related toxicity must be
             restored to common terminology criteria for adverse events (CTCAE) level 1 of the
             National Cancer Institute [NCI] before randomization.).

          9. According to the recist1.1 standard, there is at least one measurable objective tumor
             focus. The maximum diameter of spiral CT must be ≥ 1cm, and the maximum diameter of
             normal CT or MRI must be ≥ 2cm, and it should be carried out within 28 days before
             enrollment.

         10. All eligible patients have adequate organ function. According to the following
             laboratory test results (no blood transfusion, G-CSF or other medical support
             treatment within 14 days before the drug administration). The laboratory test results
             within 1 week before the study drug administration meet the following conditions:
             (HGB≥90 g/L , PLT ≥75 × 10⁹ /L, WBC ≥ 3.0× 10⁹ /L, ANC ≥1.5× 10⁹ / L, TBI ≤1.5 times
             UNL, Cr≤1.5 times the UNL, ALT and AST ≤2.5 times UNL(5 times UNL )in case of liver
             metastasis.

         11. Subjects with active hepatitis B or active hepatitis C must receive antiviral
             treatment for at least 14 days before the administration of the first study drug, and
             pass the detection of hepatitis B virus (HBV) DNA titer (no more than 500 IU / ml or
             2500 copies [CPS] / ml) and hepatitis C virus (HCV) RNA (no more than the detection
             limit of the detection method), which can be included in the group test, and are
             willing to continue to receive effective antiviral treatment during the study period.

         12. Patients participate voluntarily and sign written informed consent

        Exclusion Criteria:

        1.Severe hepatorenal insufficiency or history of myocardial infarction (within 3 months).

        2.5-year history of other malignancies(except skin basal cell carcinoma, cervical carcinoma
        in situ).

        3.Subjects with active or previous autoimmune diseases or risks that may recur(eg:requiring
        immunosuppressive therapy for organ transplantation). However, subjects with type I
        diabetes, hypothyroidism requiring hormone replacement therapy only, or skin diseases
        without systemic treatment (such as vitiligo, psoriasis, or alopecia) were allowed to enter
        the group.

        4.Have had interstitial lung disease or noninfective pneumonia, etc. symptoms of the
        disease or previous lung history may hinder the assessment or management of lung toxicity
        related to the study drug.

        5.Before the first administration of the study drug and who had a history of active
        tuberculosis infection more than one year ago were considered suitable for inclusion if
        they were judged by the investigator to have no evidence of active tuberculosis at present.

        6.Severe uncontrolled medical disease or acute infection (fever above 38 ℃ caused by
        infection).

        7.The combination of serious internal and external diseases, affecting organ function, the
        researchers think it is not suitable to participate in this clinical trial.

        8.Pregnant or lactating women or fertile (men or women with menopause less than 1 year) are
        unwilling to take contraceptive measures.

        9.Patients with a long history of chronic diarrhea or complete intestinal obstruction.

        10.Subjects requiring systemic treatment with corticosteroids (> 10 mg / day equivalent of
        prednisone) or other immunosuppressive drugs within 14 days prior to administration of the
        study drug. Note: if there is no active autoimmune disease, it is allowed to use inhaled or
        local steroid hormone, or adrenaline replacement therapy with equivalent dose of prednisone
        ≤ 10 mg per day. Short term (< 7 days) use of glucocorticoids for prophylactic treatment
        (e.g. contrast agent allergy) or for treatment of non autoimmune diseases (e.g. delayed
        type hypersensitivity caused by contact allergens) is allowed.

        11.Have interstitial lung disease or noninfective pneumonia, etc. symptoms of the disease
        or previous lung history may hinder the assessment or management of lung toxicity related
        to the study drug.

        12.Subjects who have received any antibody / drug (such as anti-PD-1, anti-PD- L1,
        anti-CTLA-4, anti OX-40, anti-CD137, anti Tim-3, anti LAG-3 antibody, etc.) targeting
        T-cell co regulatory protein (immunocheckpoint).

        13.Subjects with a history of hypersensitivity or hypersensitivity to study drug
        components.

        14.unable to take oral medicine.

        15.Presence of immunodeficient disease or HIV infection.

        16.Patients not suitable for this clinical trial determined by the investigator
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:12-month Progression Free Survival rate
Time Frame:Up to 12 months
Safety Issue:
Description:Proportion of patients with Progression Free Survival in 12-month

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 12 months
Safety Issue:
Description:Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
Measure:R0 resection rate
Time Frame:Up to 12 months
Safety Issue:
Description:Proportion of patients with complete resection
Measure:Tumor Regression Grading
Time Frame:Up to 12 months
Safety Issue:
Description:Assessing the grade of tumor regression according to tumor regression grading criteria
Measure:Progression Free Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Defined as the time from the date of enrollment to the first date of documented objective progression disease (defined by RECIST 1.1) or of death from any cause
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Defined as the time from the date of enrollment to the date of death from any cause
Measure:Incidence of Treatment-Emergent Adverse Event
Time Frame:Up to 12 months
Safety Issue:
Description:Any adverse events related with treatment with Sintilimab plus CAPOX

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sichuan University

Trial Keywords

  • adenocarcinoma of the stomach or esophagogastric junction
  • conversion therapy
  • Sintilimab
  • CAPOX
  • unresectable locally advanced
  • limited metastasis

Last Updated

February 8, 2020