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Thalidomide Combined With Chemotherapy and Monotherapy for Maintenance Treatment for Her2-negative Advanced GC

Primary Purpose

Gastric Cancer Metastatic to Liver

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Thalidomide Combined With Chemotherapy and Monotherapy
Sponsored by
Qilu Hospital of Shandong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer Metastatic to Liver focused on measuring Thalidomide, maintenance treatment, gastric cancer, liver metastases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Aged 18-75 years old;
  2. ECOG physical status score 0-1 points (within 3 days before starting treatment);
  3. Expected survival period ≥ 3 months;
  4. Basically normal functions of major organs;
  5. Pathologically confirmed metastatic gastric cancer or adenocarcinoma at the gastroesophageal junction with no chance of radical surgery, accompanied by liver metastasis or simple liver metastasis;
  6. No previous medical treatment; If neoadjuvant or adjuvant chemotherapy has been performed before and after surgery, recurrence can be defined as first-line therapy only after drug withdrawal for at least six months;
  7. HER2 negative. HER2 negative definition: IHC (0 or 1+), or IHC (2+) but negative for FISH (HER2:CEP17<2 with mean HER2 copy number <4.0 signals/cell);
  8. Measurable lesions assessed according to RECIST1.1;
  9. Able to swallow pills normally.

Exclusion Criteria:

  1. Those who are allergic to thalidomide;
  2. Pregnant or lactating women;
  3. Severe mental illness;
  4. Those who cannot take medication or follow up as planned;
  5. During the trial period and within 3 months after the trial, the subjects and their partners are not willing to use contraception;
  6. Participants in other clinical studies 3 months prior to the trial;
  7. Patients who are financially well off and willing to use immune checkpoint inhibitors.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Thalidomide

    Arm Description

    The study is divided into two phases: The first phase is a combination phase (chemotherapy +T) : Oxaliplatin (130mg/m2 iv d1) and capecitabine (1000mg/m2 d1-14 po bid) repeated every 21 days for a total of 4-6 cycles. Thalidomide tablet: 100 mg/d, qn, orally. The second stage is maintenance stage: Patients who have obtained CR, PR or SD in the first stage enter the maintenance stage and receive maintenance treatment with thalidomide tablets: 100mg/d, qn, orally. Maintained until disease progression or adverse reactions are intolerable.

    Outcomes

    Primary Outcome Measures

    progression-free survival (PFS)
    PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).

    Secondary Outcome Measures

    Quality of life (QOL)
    EORTC QLQ-C30 (Version 3) Quality of life questionnaire will be used to assess the quality of life of the subjects.
    Percentage of Participants With Adverse Events (AEs)
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Full Information

    First Posted
    November 18, 2021
    Last Updated
    January 17, 2022
    Sponsor
    Qilu Hospital of Shandong University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05198856
    Brief Title
    Thalidomide Combined With Chemotherapy and Monotherapy for Maintenance Treatment for Her2-negative Advanced GC
    Official Title
    A Single-arm, Open, Prospective, Multi-center Study on Thalidomide Combined With First-line Chemotherapy and Monotherapy for Maintenance Treatment of Liver Metastases From Her2-negative Advanced Gastric Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 10, 2022 (Anticipated)
    Primary Completion Date
    March 10, 2024 (Anticipated)
    Study Completion Date
    December 10, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Qilu Hospital of Shandong University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging. Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN. Therefore, it is very meaningful to explore the therapeutic value of thalidomide in advanced gastric cancer liver metastasis.
    Detailed Description
    The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging. Although immune checkpoint inhibitors have been approved for third-line treatment of advanced gastric cancer, they are expensive and poorly accessible. For patients with poor economic conditions, combination therapy based on chemotherapy regimen or treatment regimen optimization may still be a relatively important direction. Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN. In addition, the sedative effect of thalidomide helps to improve patients' sleep. Thalidomide can also inhibit inflammatory factors such as TNF-α, thus improving appetite and increasing lean body weight in patients with cachexia. Its antiemetic effects can reduce gastrointestinal reactions to chemotherapeutic drugs in combined therapy. Thalidomide is also very cheap in China, which is suitable for patients on long-term maintenance treatment. Therefore, it is of great significance to explore the therapeutic value of thalidomide in liver metastasis of advanced gastric cancer.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer Metastatic to Liver
    Keywords
    Thalidomide, maintenance treatment, gastric cancer, liver metastases

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    106 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Thalidomide
    Arm Type
    Experimental
    Arm Description
    The study is divided into two phases: The first phase is a combination phase (chemotherapy +T) : Oxaliplatin (130mg/m2 iv d1) and capecitabine (1000mg/m2 d1-14 po bid) repeated every 21 days for a total of 4-6 cycles. Thalidomide tablet: 100 mg/d, qn, orally. The second stage is maintenance stage: Patients who have obtained CR, PR or SD in the first stage enter the maintenance stage and receive maintenance treatment with thalidomide tablets: 100mg/d, qn, orally. Maintained until disease progression or adverse reactions are intolerable.
    Intervention Type
    Drug
    Intervention Name(s)
    Thalidomide Combined With Chemotherapy and Monotherapy
    Other Intervention Name(s)
    Fanyingting
    Intervention Description
    Combined period:chemotherapy + T :Thalidomide tablets: 100mg/d Maintenance period: 100 mg/d, qn, orally. Sustained to disease progression or intolerable adverse reactions.
    Primary Outcome Measure Information:
    Title
    progression-free survival (PFS)
    Description
    PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
    Time Frame
    Randomization to the first occurrence of disease progression or death from any cause up to the clinical cut off date of March10,2024 (up to approximately 18 months) ]
    Secondary Outcome Measure Information:
    Title
    Quality of life (QOL)
    Description
    EORTC QLQ-C30 (Version 3) Quality of life questionnaire will be used to assess the quality of life of the subjects.
    Time Frame
    UpUp to end of study (up to approximately 24 months)
    Title
    Percentage of Participants With Adverse Events (AEs)
    Description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
    Time Frame
    Up to end of study (up to approximately 24 months)

    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: Aged 18-75 years old; ECOG physical status score 0-1 points (within 3 days before starting treatment); Expected survival period ≥ 3 months; Basically normal functions of major organs; Pathologically confirmed metastatic gastric cancer or adenocarcinoma at the gastroesophageal junction with no chance of radical surgery, accompanied by liver metastasis or simple liver metastasis; No previous medical treatment; If neoadjuvant or adjuvant chemotherapy has been performed before and after surgery, recurrence can be defined as first-line therapy only after drug withdrawal for at least six months; HER2 negative. HER2 negative definition: IHC (0 or 1+), or IHC (2+) but negative for FISH (HER2:CEP17<2 with mean HER2 copy number <4.0 signals/cell); Measurable lesions assessed according to RECIST1.1; Able to swallow pills normally. Exclusion Criteria: Those who are allergic to thalidomide; Pregnant or lactating women; Severe mental illness; Those who cannot take medication or follow up as planned; During the trial period and within 3 months after the trial, the subjects and their partners are not willing to use contraception; Participants in other clinical studies 3 months prior to the trial; Patients who are financially well off and willing to use immune checkpoint inhibitors.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiuwen Wang, MD. PhD
    Phone
    +86 13791123979
    Email
    wangxiuwen@medmail.com.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Cuihua Yi, MD. PhD
    Phone
    +86 18560082871
    Email
    yicuihua@sdu.edu.cn

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
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    27447571
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    Thalidomide Combined With Chemotherapy and Monotherapy for Maintenance Treatment for Her2-negative Advanced GC

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