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Etoposide/Cisplatin Compared With Irinotecan/Cisplatin for Advanced Gastrointestinal Neuroendocrine Tumor G3 Type

Primary Purpose

Gastrointestinal Neuroendocrine Tumor

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Etoposide
Irinotecan
Sponsored by
Henan Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Neuroendocrine Tumor

Eligibility Criteria

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

Inclusion Criteria:

  • 1. 18-75 years old, male or female. 2. Confirmed non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type patients by histopathological and imaging examinations.

    3. ECOG performance status 0-1. 4. Life expectancy ≥ 12 weeks. 5. A histological specimen can be provided for secondary testing. 6. According to the evaluation criteria of solid tumor efficacy (RESIST 1.1), there should be at least one measurable lesion (empty organs such as esophagus and stomach cannot be taken as the measurable lesion), and the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area is also selected as the target lesion if the lesion progression is confirmed).

    7. Never received system treatment before, including cytotoxic drugs. For patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or metastasis more than 6 months from accepting the last dose of chemotherapy drugs can be screened.

    8. The main organ function meets the following criteria within 7 days before treatment:

    1. Blood routine examination criteria (without blood transfusion within 14 days): hemoglobin (HB) ≥ 90g/L, the absolute value of neutrophils (ANC) ≥ 1.5 x 10^9/L, platelet (PLT) ≥ 80 x 10^9/L.
    2. Biochemical examinations must meet the following criteria: total bilirubin (TBIL) ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN, serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance (CCR) ≥ 60 mL/min.
    3. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%).

    9. Fertile men and women must use effective contraception during the study period and within 6 months after the end of the study.

    10. Volunteered to participate in the study and signed an informed consent form.

Exclusion Criteria:

  • 1.Patients exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in site, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumor), Tis (in situ carcinoma), and T1 (tumor infiltrating basement membrane)); Patients with rapid progress within 3 months.

    2. History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration.

    3. Patients who had received radiotherapy for tumor target lesions within 4 weeks before enrollment.

    4. History of immunodeficiency disease, including HIV positive and other acquired or congenital immunodeficiency diseases.

    5. Allergic reactions and drug adverse reactions:

    1. A history of allergy to the ingredients of the study drug;
    2. Any contraindication to any study drug (etoposide, irinotecan and cis-platinum) in the chemotherapy regimen.

    6. Significantly malnourished patients. Exclusion is performed if the patient is receiving intravenous fluids or is required to be hospitalized for continuous infusion therapy. Patients with good nutrition control ≥ 28 days can be enrolled before randomization.

    7. Any severe and/or uncontrolled disease, including:

    1. Patients with hypertension whose blood can't be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg).
    2. Grade 1 or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480 ms) or grade 2 and above congestive heart failure according to New York Heart Association (MYHA) classification.
    3. Severe or uncontrolled disease or active infection (≥ CTC AE grade 2), which the investigators believe may increase the risk associated with patient participation and drug administration.
    4. Renal failure requiring hemodialysis or peritoneal dialysis.
    5. Patients of diabetes who have poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L).
    6. Patients of seizures requiring treatment. 8. Patients with gastrointestinal disease such as intestinal obstruction (including incomplete intestinal obstruction) or those who may meet gastrointestinal bleeding, perforation obstruction.

    9. Patients who underwent surgical treatment, incision biopsy or significant traumatic injury within 28 days prior to enrollment.

    10. Any bleeding event ≥ CTC AE grade 3 or unhealed wounds, ulcers or fractures in 4 weeks prior to enrollment.

    11. Arterial/venous thrombosis events within 3 months, such as cerebrovascular accidents (including transient ischemic attacks), deep venous thrombosis and pulmonary embolism.

    12. Patients who prepared or accepted previously allogeneic organ or bone marrow transplantation, including liver transplantation.

    13. Concomitant disease that seriously harms the patient's safety or affects the patient's completion of the study according to the investigator's judgment.

    14. Patients cannot provide histological specimens for secondary test. 15. Patients who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder.

    16. Urine routine showed urinary protein ≥ 2 + and 24-hour urine protein quantitation > 1.0 g.

    17. Patients with brain metastases. 18. Patients who have participated in other anti-tumor drug clinical trials within 4 weeks.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Etoposide plus Cisplatin

    Irinotecan plus Cisplatin

    Arm Description

    Etoposide 100mg/m^2 ivggt on days 1, 2, 3, Cisplatin 25mg/m^2 ivggt on days 1, 2, 3, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.

    Irinotecan 65 mg/m^2 ivggt on days 1, 8, Cisplatin 30 mg/m^2 ivggt on days 1, 8, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.

    Outcomes

    Primary Outcome Measures

    Objective response rate (ORR)
    To compare objective response rate of the two arms from date of anti-cancer therapy until progression
    Progression-free Survival (PFS)
    From the first day of treatment until the date of first documented progression or date of death from any cause

    Secondary Outcome Measures

    Overall survival (OS)
    From the first day of treatment to death or last survival confirm date
    Number of Participants with Treatment-related Adverse Events
    Treatment-related adverse events will be assessed by CT CAE v4.0
    Assessment of Health-related quality of life
    Quality of Life Questionnaire (QLQ-C30) will be evaluated since treatment begins. At the end of the trail, the differences between the two indicators will be compared with Mixed-effects model repeated measures (MMRM), where the baseline is scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline will be statistically described.

    Full Information

    First Posted
    May 20, 2019
    Last Updated
    May 23, 2019
    Sponsor
    Henan Cancer Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03963193
    Brief Title
    Etoposide/Cisplatin Compared With Irinotecan/Cisplatin for Advanced Gastrointestinal Neuroendocrine Tumor G3 Type
    Official Title
    Phase II Trial of Etoposide Plus Cisplatin Compared With Irinotecan Plus Cisplatin for First-line Treatment of Non-primary Pancreatic Metastatic and/or Unresectable Gastrointestinal Neuroendocrine Tumor G3 Type
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    June 1, 2019 (Anticipated)
    Primary Completion Date
    June 1, 2020 (Anticipated)
    Study Completion Date
    June 1, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Henan Cancer Hospital

    4. Oversight

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

    5. Study Description

    Brief Summary
    The aim of this study is to investigate the efficacy, safety, and survival benefit of etoposide plus cisplatin and irinotecan plus cisplatin in first-line therapy of non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type. In addition, the investigators will explore the resistance mechanisms of gastrointestinal neuroendocrine tumor G3, and screen out biomarkers that can predict the efficacy of chemotherapy.
    Detailed Description
    The prognosis of gastrointestinal neuroendocrine tumor G3 type patients who cannot be surgically resected is poor. The median overall survival (OS) is only 6-10 months, and the 3-year survival rate is less than 10%. Among the neuroendocrine tumors of the digestive system, only pancreatic neuroendocrine tumor has a standard treatment strategy, and there is a lack of prospective clinical research data on other gastrointestinal neuroendocrine tumors. According to the chemotherapy regimen of small cell lung cancer, etoposide plus cisplatin or irinotecan plus cisplatin is the choice of rescue therapy for advanced non-surgical or metastatic neuroendocrine tumor G3 type. However, prospective studies are needed to confirm whether there are differences in efficacy and safety between the two chemotherapy regimens. The aim of this study is to investigate the efficacy, safety, and survival benefit of etoposide plus cisplatin and irinotecan plus cisplatin in first-line therapy of non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type. In addition, the investigators will explore the resistance mechanisms of gastrointestinal neuroendocrine tumor G3, and screen out biomarkers that can predict the efficacy of chemotherapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastrointestinal Neuroendocrine Tumor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    112 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Etoposide plus Cisplatin
    Arm Type
    Experimental
    Arm Description
    Etoposide 100mg/m^2 ivggt on days 1, 2, 3, Cisplatin 25mg/m^2 ivggt on days 1, 2, 3, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.
    Arm Title
    Irinotecan plus Cisplatin
    Arm Type
    Experimental
    Arm Description
    Irinotecan 65 mg/m^2 ivggt on days 1, 8, Cisplatin 30 mg/m^2 ivggt on days 1, 8, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.
    Intervention Type
    Drug
    Intervention Name(s)
    Etoposide
    Other Intervention Name(s)
    Cisplatin
    Intervention Description
    Etoposide 100mg/m^2 ivggt on days 1, 2, 3, Cisplatin 25mg/m^2 ivggt on days 1, 2, 3, repeated every 21 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Irinotecan
    Other Intervention Name(s)
    Cisplatin
    Intervention Description
    Irinotecan 65 mg/m^2 ivggt on days 1, 8, Cisplatin 30 mg/m^2 ivggt on days 1, 8, repeated every 21 days.
    Primary Outcome Measure Information:
    Title
    Objective response rate (ORR)
    Description
    To compare objective response rate of the two arms from date of anti-cancer therapy until progression
    Time Frame
    up to 2 years
    Title
    Progression-free Survival (PFS)
    Description
    From the first day of treatment until the date of first documented progression or date of death from any cause
    Time Frame
    up to 2 years
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    From the first day of treatment to death or last survival confirm date
    Time Frame
    up to 2 years
    Title
    Number of Participants with Treatment-related Adverse Events
    Description
    Treatment-related adverse events will be assessed by CT CAE v4.0
    Time Frame
    up to 2 years
    Title
    Assessment of Health-related quality of life
    Description
    Quality of Life Questionnaire (QLQ-C30) will be evaluated since treatment begins. At the end of the trail, the differences between the two indicators will be compared with Mixed-effects model repeated measures (MMRM), where the baseline is scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline will be statistically described.
    Time Frame
    up to 2 years

    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: 1. 18-75 years old, male or female. 2. Confirmed non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type patients by histopathological and imaging examinations. 3. ECOG performance status 0-1. 4. Life expectancy ≥ 12 weeks. 5. A histological specimen can be provided for secondary testing. 6. According to the evaluation criteria of solid tumor efficacy (RESIST 1.1), there should be at least one measurable lesion (empty organs such as esophagus and stomach cannot be taken as the measurable lesion), and the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area is also selected as the target lesion if the lesion progression is confirmed). 7. Never received system treatment before, including cytotoxic drugs. For patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or metastasis more than 6 months from accepting the last dose of chemotherapy drugs can be screened. 8. The main organ function meets the following criteria within 7 days before treatment: Blood routine examination criteria (without blood transfusion within 14 days): hemoglobin (HB) ≥ 90g/L, the absolute value of neutrophils (ANC) ≥ 1.5 x 10^9/L, platelet (PLT) ≥ 80 x 10^9/L. Biochemical examinations must meet the following criteria: total bilirubin (TBIL) ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN, serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance (CCR) ≥ 60 mL/min. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%). 9. Fertile men and women must use effective contraception during the study period and within 6 months after the end of the study. 10. Volunteered to participate in the study and signed an informed consent form. Exclusion Criteria: 1.Patients exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in site, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumor), Tis (in situ carcinoma), and T1 (tumor infiltrating basement membrane)); Patients with rapid progress within 3 months. 2. History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration. 3. Patients who had received radiotherapy for tumor target lesions within 4 weeks before enrollment. 4. History of immunodeficiency disease, including HIV positive and other acquired or congenital immunodeficiency diseases. 5. Allergic reactions and drug adverse reactions: A history of allergy to the ingredients of the study drug; Any contraindication to any study drug (etoposide, irinotecan and cis-platinum) in the chemotherapy regimen. 6. Significantly malnourished patients. Exclusion is performed if the patient is receiving intravenous fluids or is required to be hospitalized for continuous infusion therapy. Patients with good nutrition control ≥ 28 days can be enrolled before randomization. 7. Any severe and/or uncontrolled disease, including: Patients with hypertension whose blood can't be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg). Grade 1 or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480 ms) or grade 2 and above congestive heart failure according to New York Heart Association (MYHA) classification. Severe or uncontrolled disease or active infection (≥ CTC AE grade 2), which the investigators believe may increase the risk associated with patient participation and drug administration. Renal failure requiring hemodialysis or peritoneal dialysis. Patients of diabetes who have poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L). Patients of seizures requiring treatment. 8. Patients with gastrointestinal disease such as intestinal obstruction (including incomplete intestinal obstruction) or those who may meet gastrointestinal bleeding, perforation obstruction. 9. Patients who underwent surgical treatment, incision biopsy or significant traumatic injury within 28 days prior to enrollment. 10. Any bleeding event ≥ CTC AE grade 3 or unhealed wounds, ulcers or fractures in 4 weeks prior to enrollment. 11. Arterial/venous thrombosis events within 3 months, such as cerebrovascular accidents (including transient ischemic attacks), deep venous thrombosis and pulmonary embolism. 12. Patients who prepared or accepted previously allogeneic organ or bone marrow transplantation, including liver transplantation. 13. Concomitant disease that seriously harms the patient's safety or affects the patient's completion of the study according to the investigator's judgment. 14. Patients cannot provide histological specimens for secondary test. 15. Patients who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder. 16. Urine routine showed urinary protein ≥ 2 + and 24-hour urine protein quantitation > 1.0 g. 17. Patients with brain metastases. 18. Patients who have participated in other anti-tumor drug clinical trials within 4 weeks.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ying Liu
    Phone
    13783604602
    Email
    yaya7207@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Baoxia He
    Organizational Affiliation
    Henan Cancer Hospital
    Official's Role
    Study Director

    12. IPD Sharing Statement

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