Trial Title:
Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and PCSK9 Inhibitor for pMMR/MSS Locally Advanced Mid-low Rectal Cancer
NCT ID:
NCT06304987
Condition:
Locally Advanced Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Immune Checkpoint Inhibitors
PCSK9 Inhibitors
Conditions: Keywords:
pMMR/MSS
PD-1
PCSK9
chemoradiation
neoadjuvant
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Experimental: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and PCSK9
inhibitor Control: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor
Description:
In long-course chemoradiotherapy (CRT) + PD-1 inhibitor for LARC patients, the
experimental group used concurrent PCSK9 inhibitor, and the active comparison group did
not use PCSK9 inhibitor.
Arm group label:
CRT+PD-1 inhibitor
Intervention type:
Combination Product
Intervention name:
Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor
Description:
In long-course chemoradiotherapy (CRT) + PD-1 inhibitor for LARC patients, the
experimental group used concurrent PCSK9 inhibitor, and the active comparison group did
not use PCSK9 inhibitor.
Arm group label:
CRT+PD-1 inhibitor+PCSK9 inhibitor
Summary:
This is a multicenter, prospective, randomized controlled study to evaluate the
effectiveness and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor
and PCSK9 inhibitor in the treatment of patients with pMMR/MSS locally advanced middle
and low rectal cancer.
Detailed description:
This study included patients with locally advanced low rectal cancer as research
subjects, and evaluated the efficacy and safety of neoadjuvant chemoradiotherapy combined
with PD-1 inhibitor (Sintilimab) and PCSK9 inhibitor (Tafolecimab) or neoadjuvant
chemoradiotherapy combined with PD -1 (Sintilimab) for patients with locally advanced
rectal cancer. The primary endpoints of the study are clinical complete response (cCR)
(including imaging and endoscopic complete response) and pathological complete response
(pCR). Secondary endpoints are major pathological response rate (MPR), objective response
rate (ORR), disease-free survival (DFS), overall survival (OS), organ preservation rate
(OPR), and neoadjuvant rectal (NAR) score, quality of life score (QoL), safety and
tolerability.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign a written informed consent form and voluntarily join this study;
2. Age 18-75 years old, male or female;
3. Pathologically confirmed adenocarcinoma of the rectum;
4. Clinically staged as II~III stage by MRI (according to the 8th edition of AJCC);
5. Tumor lower edge distance from the anal margin ≤10cm;
6. Able to undergo surgical resection;
7. Able to swallow pills normally;
8. ECOG PS 0-1;
9. No prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy,
surgery, etc.;
10. Planning to undergo surgical treatment after completing neoadjuvant therapy;
11. No contraindications for surgery;
12. Normal major organ function, including:
1. Blood routine examination (no blood or blood products transfusion within 14
days before the first treatment, no use of G-CSF or other hematopoietic
stimulating factors for correction):
- Neutrophil count ≥1.5×109/L
- Platelet count ≥100×109/L
- Hemoglobin ≥90 g/L
2. Blood biochemistry:
- Total bilirubin ≤1.5×ULN
- ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN,
- Serum creatinine ≤1.5×ULN, or creatinine clearance rate ≥50 mL/min
(Cocheroft-Gault formula)
3. Coagulation function:
- International normalized ratio (INR) ≤ 1.5×ULN
- Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
- Female subjects of childbearing potential should have a negative serum
pregnancy test within 72 hours before the start of study drug
administration, and effective contraception should be used during the
trial period and for at least 3 months after the last dose (such as
intrauterine devices, contraceptive pills, or condoms); for male subjects
with female partners of childbearing potential, effective contraception
should be used during the trial period and for 3 months after the last
dose.
Exclusion Criteria:
1. History of allergy to monoclonal antibodies, PD-1 monoclonal antibodies,
capecitabine, or oxaliplatin;
2. History of receiving or currently receiving any of the following treatments:
1. Any surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.,
for tumors;
2. Use of immunosuppressive drugs or systemic steroid therapy to achieve
immunosuppression (dose >10mg/day prednisone or equivalent) within 2 weeks
before the first use of the study drug; inhalation or local use of steroids and
adrenal cortical hormone replacement therapy with a dose >10mg/day prednisone
or equivalent is allowed in the absence of active autoimmune diseases;
3. Receipt of attenuated live vaccines within 4 weeks before the first use of the
study drug;
4. Underwent major surgery or had severe trauma within 4 weeks before the first
use of the study drug;
3. Active autoimmune diseases or history of autoimmune diseases, including but not
limited to: interstitial pneumonia, enteritis, hepatitis, pituitary inflammation,
vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered for inclusion
after hormone replacement therapy); psoriasis or childhood asthma/allergies that
have completely resolved and do not require any intervention in adulthood may be
considered for inclusion, but patients requiring bronchodilators for medical
intervention are not eligible for inclusion;
4. History of immunodeficiency, including HIV positive, or acquired or congenital
immunodeficiency diseases, or history of organ transplantation or allogeneic bone
marrow transplantation;
5. Presence of poorly controlled clinical symptoms or diseases of the heart, including
but not limited to: (1) NYHA class II or above heart failure, (2) unstable angina
pectoris, (3) myocardial infarction within the past year, (4) clinically significant
supraventricular or ventricular arrhythmias that have not been clinically intervened
or poorly controlled after clinical intervention;
6. Severe infection (CTCAE > grade 2) within 4 weeks before the first use of the study
drug, such as severe pneumonia requiring hospitalization, septicemia, complications
of infection, etc.; baseline chest imaging suggests active pulmonary inflammation,
presence of symptoms and signs of infection within 14 days before the first use of
the study drug or requiring oral or intravenous antibiotic therapy, except for
prophylactic use of antibiotics;
7. Active pulmonary tuberculosis infection found through medical history or CT
examination, or a history of active pulmonary tuberculosis infection within the past
year before enrollment, or a history of active pulmonary tuberculosis infection more
than 1 year ago but without proper treatment;
8. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (HCV
antibody positive, and HCV RNA higher than the lower limit of detection of the
assay);
9. Diagnosed with other malignant tumors within 5 years before the first use of the
study drug, unless they have a low risk of metastasis or death (5-year survival rate
> 90%), such as adequately treated basal cell carcinoma or squamous cell skin cancer
or carcinoma in situ of the cervix, may be considered for inclusion;
10. Pregnant or lactating women;
11. Judged by the investigator to have other factors that may lead to premature
termination of the study, such as having other serious diseases (including mental
illnesses) requiring concomitant treatment, alcoholism, drug abuse, family or social
factors, factors that may affect the safety or compliance of the subject.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Friendship Hospital, Capital Medical University
Address:
City:
Beijing
Zip:
100050
Country:
China
Facility:
Name:
Beijing Friendship Hospital
Address:
City:
Beijing
Zip:
100050
Country:
China
Start date:
April 2024
Completion date:
May 2026
Lead sponsor:
Agency:
Beijing Friendship Hospital
Agency class:
Other
Collaborator:
Agency:
Peking Union Medical College Hospital
Agency class:
Other
Collaborator:
Agency:
Peking University Cancer Hospital & Institute
Agency class:
Other
Collaborator:
Agency:
Changhai Hospital
Agency class:
Other
Source:
Beijing Friendship Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06304987
