Trial Title:
Assess the Efficacy of Radiotherapy and Sequential Chemotherapy and AK104 Before TME Surgery for Local CRC（AK104-IIT-13）
NCT ID:
NCT05794750
Condition:
Locally Advanced Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Capecitabine
Oxaliplatin
Conditions: Keywords:
AK104
colorectal cancer
Pelvic short-course radiotherapy
TME surgery
pCR
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AK104 injection
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).
Arm group label:
AK104 injection++chemotherapy
Arm group label:
TME surgery
Arm group label:
chemotherapy
Other name:
Immunotherapy
Intervention type:
Procedure
Intervention name:
TME surgery
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).
Arm group label:
AK104 injection++chemotherapy
Arm group label:
TME surgery
Arm group label:
chemotherapy
Other name:
Surgery
Intervention type:
Drug
Intervention name:
Capecitabine
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).
Arm group label:
AK104 injection++chemotherapy
Arm group label:
TME surgery
Arm group label:
chemotherapy
Other name:
Chemotherapy drug
Intervention type:
Drug
Intervention name:
Oxaliplatin
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).
Arm group label:
AK104 injection++chemotherapy
Arm group label:
TME surgery
Arm group label:
chemotherapy
Other name:
Chemotherapy drug
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
April 24, 2023
Completion date:
April 24, 2027
Lead sponsor:
Agency:
JIN JING
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05794750
