NCT05794750

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.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_2

Timeline
12mo left

Started Apr 2023

Typical duration for phase_2

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress76%
Apr 2023Apr 2027

First Submitted

Initial submission to the registry

February 19, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 3, 2023

Completed
21 days until next milestone

Study Start

First participant enrolled

April 24, 2023

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 24, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 24, 2027

Last Updated

April 6, 2023

Status Verified

April 1, 2023

Enrollment Period

4 years

First QC Date

February 19, 2023

Last Update Submit

April 4, 2023

Conditions

Locally Advanced Rectal Cancer

Keywords

AK104colorectal cancerPelvic short-course radiotherapyTME surgerypCR

Outcome Measures

Primary Outcomes (1)

  • Pathologic complete response rate (pCR)

    To assess the result from pathology report

    From date of randomization until the date of end of treatment,about 18 weeks.

Secondary Outcomes (4)

  • Major pathologic response rate (MPR)

    From date of randomization until the date of end of treatment,about 18 weeks.

  • 3-years DFS rate

    From date of randomization until the date of first documented disease relapse or date of death from any cause, whichever came first about 3years..

  • 3-years OS rate

    From date of randomization until date of death from any cause,about 3 years.

  • Incidence and severity of adverse events (AEs) and clinically meaningful abnormal laboratory test results

    From date of randomization until the date of end of treatment,about 18 weeks.

Other Outcomes (1)

  • Relationship between the expression of immune markers in tumor tissues and blood,the distribution of immune cells, and the efficacy and prognosis of patients

    From date of randomization until the date of end of treatment,about 18 weeks.

Study Arms (3)

AK104 injection++chemotherapy

EXPERIMENTAL

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

Drug: AK104 injectionProcedure: TME surgeryDrug: CapecitabineDrug: Oxaliplatin

TME surgery

EXPERIMENTAL

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

Drug: AK104 injectionProcedure: TME surgeryDrug: CapecitabineDrug: Oxaliplatin

chemotherapy

EXPERIMENTAL

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

Drug: AK104 injectionProcedure: TME surgeryDrug: CapecitabineDrug: Oxaliplatin

Interventions

AK104 injectionDRUG

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).

Also known as: Immunotherapy
AK104 injection++chemotherapyTME surgerychemotherapy
TME surgeryPROCEDURE

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).

Also known as: Surgery
AK104 injection++chemotherapyTME surgerychemotherapy
CapecitabineDRUG

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).

Also known as: Chemotherapy drug
AK104 injection++chemotherapyTME surgerychemotherapy
OxaliplatinDRUG

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).

Also known as: Chemotherapy drug
AK104 injection++chemotherapyTME surgerychemotherapy

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. Age 18-75 years old, gender is not limited;
  • \. Stage II/III under MRI or endoscopic ultrasound ;
  • \. Fiber colonoscopy or diagnosis examination, the lower boundary of the lesion is 15m ≤ from the margin;
  • \. Rectal adenocarcinoma confirmed or revisited by pathology;
  • \. Karl Fischer score ≥ 80 points or ECOG score of 0-1;
  • \. 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.
  • \. No history of allergy to 5-Fu drugs, no history of allergy to platinum drugs;
  • \. With primary rectal cancer required to undergo surgery (except palliative ostomy), chemotherapy or other anti-tumor therapy before diagnosis to enrollment;
  • \. Not received radiation before;
  • \. Sign the informed consent form.

You may not qualify if:

  • \. Previous anti-PD-1/L1 and anti-CTLA-4 immune drugs or other immunoassay drugs;
  • \. 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.;
  • \. Symptomatic interstitial lung disease or active infection/non-infectious pneumonia;
  • \. 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;
  • \. History of other malignant tumors, excluding curable non-melanogenic skin cancer and carcinoma in situ of the cervix;
  • \. Active infection, heart failure, myocardial infarction, unstable angina or unstable arrhythmia within 6 months;
  • \. 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;
  • \. Breastfeeding or pregnant women;
  • \. Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or organ transplantation, allogeneic stem cell transplantation;
  • \. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), active tuberculosis infection;
  • \. 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)
  • \. Use other immunological agents, chemotherapy drugs, drugs in other clinical studies, and long-term cortisol therapy are not enrolled
  • \. With mental illness, substance abuse, and social problems that affect compliance will not be enrolled after a doctor's review
  • \. Allergic or contraindicated to the treatment of drugs.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Xu T, Feng L, Zhang W, Li H, Ma H, Abulimiti M, Tan Y, Deng F, Huang W, Zou S, Kang W, Jiang L, Wang Y, Hu C, Chen Y, Zhou H, Tang Y, Jin J. The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study. BMC Cancer. 2024 Apr 19;24(1):501. doi: 10.1186/s12885-024-12254-1.

    PMID: 38641773DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

ImmunotherapySurgical Procedures, OperativeCapecitabineOxaliplatin

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

ImmunomodulationBiological TherapyTherapeuticsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesCoordination ComplexesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Chief physician

Study Record Dates

First Submitted

February 19, 2023

First Posted

April 3, 2023

Study Start

April 24, 2023

Primary Completion (Estimated)

April 24, 2027

Study Completion (Estimated)

April 24, 2027

Last Updated

April 6, 2023

Record last verified: 2023-04