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Assess the Efficacy of Radiotherapy and Sequential Chemotherapy and AK104 Before TME Surgery for Local CRC(AK104-IIT-13) (AK104-IIT-13)

Primary Purpose

Locally Advanced Rectal Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
AK104 injection
TME surgery
Capecitabine
Oxaliplatin
Sponsored by
JIN JING
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring AK104, colorectal cancer, Pelvic short-course radiotherapy, TME surgery, pCR

Eligibility Criteria

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

Inclusion Criteria: 1. Age 18-75 years old, gender is not limited; 2. Stage II/III under MRI or endoscopic ultrasound ; 3. Fiber colonoscopy or diagnosis examination, the lower boundary of the lesion is 15m ≤ from the margin; 4. Rectal adenocarcinoma confirmed or revisited by pathology; 5. Karl Fischer score ≥ 80 points or ECOG score of 0-1; 6. Meet the following laboratory diagnostic indicators: hemoglobin ≥ 100g/L, white blood cell ≥ 3.5×109/L; neutrophils≥ 1.5×109/L, platelet ≥ 100×109/L; creatinine ≤ 1.0× upper limit of normal (UNL), urea nitrogen (BUN) ≤ 1.0× upper limit of normal (UNL); Alanine aminotransferase (ALT) ≤1.5× upper limit of normal (UNL); Aspartate aminotransferase (AST) ≤1.5× upper limit of normal (UNL); Alkaline phosphatase (ALP) ≤1.5× upper limit of normal (UNL); Total bilirubin (TBIL) ≤ 1.5× upper limit of normal (UNL); urine protein (-); Clotting time is normal. 7. No history of allergy to 5-Fu drugs, no history of allergy to platinum drugs; 8. With primary rectal cancer required to undergo surgery (except palliative ostomy), chemotherapy or other anti-tumor therapy before diagnosis to enrollment; 9. Not received radiation before; 10. Sign the informed consent form. Exclusion Criteria: 1. Previous anti-PD-1/L1 and anti-CTLA-4 immune drugs or other immunoassay drugs; 2. With severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.; 3. Symptomatic interstitial lung disease or active infection/non-infectious pneumonia; 4. Patients have risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer or other known risk factors for intestinal perforation; 5. History of other malignant tumors, excluding curable non-melanogenic skin cancer and carcinoma in situ of the cervix; 6. Active infection, heart failure, myocardial infarction, unstable angina or unstable arrhythmia within 6 months; 7. Physical examination or clinical laboratory findings that the investigator believes may interfere with the results or increase the patient's risk of treatment complications, or other uncontrollable diseases; 8. Breastfeeding or pregnant women; 9. Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or organ transplantation, allogeneic stem cell transplantation; 10. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), active tuberculosis infection; 11. Vaccinated against tumors, or received other vaccines within 4 weeks before starting treatment (Note: Because the seasonal influenza vaccine for injection is mostly an inactivated vaccine, it is allowed to be vaccinated, while intranasal preparations are usually live attenuated vaccines, so it is not allowed) 12. Use other immunological agents, chemotherapy drugs, drugs in other clinical studies, and long-term cortisol therapy are not enrolled 13. With mental illness, substance abuse, and social problems that affect compliance will not be enrolled after a doctor's review 14. Allergic or contraindicated to the treatment of drugs.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    AK104 injection++chemotherapy

    TME surgery

    chemotherapy

    Arm Description

    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104

    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104

    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104

    Outcomes

    Primary Outcome Measures

    Pathologic complete response rate (pCR)
    To assess the result from pathology report

    Secondary Outcome Measures

    Major pathologic response rate (MPR)
    To assess the result from pathology report
    3-years DFS rate
    To compute the length between end of treatment and relapse
    3-years OS rate
    To compute the length between end of treatment and death
    Incidence and severity of adverse events (AEs) and clinically meaningful abnormal laboratory test results
    To assess the result from inspection paper during the trail

    Full Information

    First Posted
    February 19, 2023
    Last Updated
    April 4, 2023
    Sponsor
    JIN JING
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05794750
    Brief Title
    Assess the Efficacy of Radiotherapy and Sequential Chemotherapy and AK104 Before TME Surgery for Local CRC(AK104-IIT-13)
    Acronym
    AK104-IIT-13
    Official Title
    A Single-arm, Multicenter, Phase II Study Evaluating the Efficacy and Safety of Preoperative Short-course Radiotherapy Followed by Sequential Chemotherapy and AK104 for Locally Advanced Rectal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 24, 2023 (Anticipated)
    Primary Completion Date
    April 24, 2027 (Anticipated)
    Study Completion Date
    April 24, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    JIN JING

    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
    This study is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of preoperative short-course radiotherapy combined with AK104 and chemotherapy + TME surgery in patients with advanced rectal cancer.
    Detailed Description
    Studies included a screening period (no more than 28 days after participants signed informed consent form to 28 days before first dose), treatment (receiving appropriate treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death or study end, whichever occurs first), and follow-up (including safety follow-up and survival follow-up). Eligible subjects will receive short-course radiotherapy (SCRT), IMRT/VMAT, pelvic 25Gy/5f/1 week. Two weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: AK104 10 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed). Patients are not recommended to enter the organ preservation observation; If the efficacy after preoperative chemoradiotherapy is evaluated as clinical complete remission (cCR) and the patient strongly refuses surgery, the patient should be informed of the risk of recurrence and ask the patient to sign a rejection of surgery. Medication safety is assessed and, depending on the severity of adverse events (AEs) and drug relevance, investigators will take steps to ensure subject safety. After surgery (or patients who strongly refuse surgery) there is a 30- and 90-day safety follow-up, and survival assessments are performed every 3 months to obtain survival information and collect new tumor treatment information until the death of the participant, withdrawal of informed consent, or the end of the study, whichever occurs first.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Locally Advanced Rectal Cancer
    Keywords
    AK104, colorectal cancer, Pelvic short-course radiotherapy, TME surgery, pCR

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    AK104 injection++chemotherapy
    Arm Type
    Experimental
    Arm Description
    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104
    Arm Title
    TME surgery
    Arm Type
    Experimental
    Arm Description
    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104
    Arm Title
    chemotherapy
    Arm Type
    Experimental
    Arm Description
    Local CRC with short-course radiotherapy followed by sequential chemotherapy and AK104
    Intervention Type
    Drug
    Intervention Name(s)
    AK104 injection
    Other Intervention Name(s)
    Immunotherapy
    Intervention Description
    Eligible subjects will receive short-course radiotherapy (SCRT), IMRT/VMAT, pelvic 25Gy/5f/1 week. Two weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: AK104 10 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed).
    Intervention Type
    Procedure
    Intervention Name(s)
    TME surgery
    Other Intervention Name(s)
    Surgery
    Intervention Description
    Eligible subjects will receive short-course radiotherapy (SCRT), IMRT/VMAT, pelvic 25Gy/5f/1 week. Two weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: AK104 10 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed).
    Intervention Type
    Drug
    Intervention Name(s)
    Capecitabine
    Other Intervention Name(s)
    Chemotherapy drug
    Intervention Description
    Eligible subjects will receive short-course radiotherapy (SCRT), IMRT/VMAT, pelvic 25Gy/5f/1 week. Two weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: AK104 10 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed).
    Intervention Type
    Drug
    Intervention Name(s)
    Oxaliplatin
    Other Intervention Name(s)
    Chemotherapy drug
    Intervention Description
    Eligible subjects will receive short-course radiotherapy (SCRT), IMRT/VMAT, pelvic 25Gy/5f/1 week. Two weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: AK104 10 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed).
    Primary Outcome Measure Information:
    Title
    Pathologic complete response rate (pCR)
    Description
    To assess the result from pathology report
    Time Frame
    From date of randomization until the date of end of treatment,about 18 weeks.
    Secondary Outcome Measure Information:
    Title
    Major pathologic response rate (MPR)
    Description
    To assess the result from pathology report
    Time Frame
    From date of randomization until the date of end of treatment,about 18 weeks.
    Title
    3-years DFS rate
    Description
    To compute the length between end of treatment and relapse
    Time Frame
    From date of randomization until the date of first documented disease relapse or date of death from any cause, whichever came first about 3years..
    Title
    3-years OS rate
    Description
    To compute the length between end of treatment and death
    Time Frame
    From date of randomization until date of death from any cause,about 3 years.
    Title
    Incidence and severity of adverse events (AEs) and clinically meaningful abnormal laboratory test results
    Description
    To assess the result from inspection paper during the trail
    Time Frame
    From date of randomization until the date of end of treatment,about 18 weeks.
    Other Pre-specified Outcome Measures:
    Title
    Relationship between the expression of immune markers in tumor tissues and blood,the distribution of immune cells, and the efficacy and prognosis of patients
    Description
    To use PCR to check the immune markers in blood and use immunofluorescent cytochemical techniques to check the immune markers in tumor tissues.The concentration of antigens and antibodies in the blood is measured to determine the efficacy and concentration of the drug after the subject's medication
    Time Frame
    From date of randomization until the date of end of treatment,about 18 weeks.

    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. Age 18-75 years old, gender is not limited; 2. Stage II/III under MRI or endoscopic ultrasound ; 3. Fiber colonoscopy or diagnosis examination, the lower boundary of the lesion is 15m ≤ from the margin; 4. Rectal adenocarcinoma confirmed or revisited by pathology; 5. Karl Fischer score ≥ 80 points or ECOG score of 0-1; 6. Meet the following laboratory diagnostic indicators: hemoglobin ≥ 100g/L, white blood cell ≥ 3.5×109/L; neutrophils≥ 1.5×109/L, platelet ≥ 100×109/L; creatinine ≤ 1.0× upper limit of normal (UNL), urea nitrogen (BUN) ≤ 1.0× upper limit of normal (UNL); Alanine aminotransferase (ALT) ≤1.5× upper limit of normal (UNL); Aspartate aminotransferase (AST) ≤1.5× upper limit of normal (UNL); Alkaline phosphatase (ALP) ≤1.5× upper limit of normal (UNL); Total bilirubin (TBIL) ≤ 1.5× upper limit of normal (UNL); urine protein (-); Clotting time is normal. 7. No history of allergy to 5-Fu drugs, no history of allergy to platinum drugs; 8. With primary rectal cancer required to undergo surgery (except palliative ostomy), chemotherapy or other anti-tumor therapy before diagnosis to enrollment; 9. Not received radiation before; 10. Sign the informed consent form. Exclusion Criteria: 1. Previous anti-PD-1/L1 and anti-CTLA-4 immune drugs or other immunoassay drugs; 2. With severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.; 3. Symptomatic interstitial lung disease or active infection/non-infectious pneumonia; 4. Patients have risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer or other known risk factors for intestinal perforation; 5. History of other malignant tumors, excluding curable non-melanogenic skin cancer and carcinoma in situ of the cervix; 6. Active infection, heart failure, myocardial infarction, unstable angina or unstable arrhythmia within 6 months; 7. Physical examination or clinical laboratory findings that the investigator believes may interfere with the results or increase the patient's risk of treatment complications, or other uncontrollable diseases; 8. Breastfeeding or pregnant women; 9. Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or organ transplantation, allogeneic stem cell transplantation; 10. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), active tuberculosis infection; 11. Vaccinated against tumors, or received other vaccines within 4 weeks before starting treatment (Note: Because the seasonal influenza vaccine for injection is mostly an inactivated vaccine, it is allowed to be vaccinated, while intranasal preparations are usually live attenuated vaccines, so it is not allowed) 12. Use other immunological agents, chemotherapy drugs, drugs in other clinical studies, and long-term cortisol therapy are not enrolled 13. With mental illness, substance abuse, and social problems that affect compliance will not be enrolled after a doctor's review 14. Allergic or contraindicated to the treatment of drugs.

    12. IPD Sharing Statement

    Learn more about this trial

    Assess the Efficacy of Radiotherapy and Sequential Chemotherapy and AK104 Before TME Surgery for Local CRC(AK104-IIT-13)

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