Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and PCSK9 Inhibitor for pMMR/MSS Locally Advanced Mid-low Rectal Cancer

NCT06304987 | Not Yet Recruiting Phase 2

• 1 other identifier: BFH-niCRT-05
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Locally Advanced Rectal Cancer

Keywords

pMMR/MSS; PD-1; PCSK9; chemoradiation; neoadjuvant

Outcome Measures

Primary Outcomes (2)

• CR

  complete response rate=(number of pathological complete responses + number of clinical complete responses)/total number of patients

  pCR :within 10 days after surgery;cCR :12-13 weeks after radiotherapy ends

• AE rate

  Adverse event rate

  during treatment

Secondary Outcomes (4)

• NAR score

  within 10 days after surgery

• OPR

  immediately after surgery

• ORR

  within 10 days after surgery

• immune-related adverse event rate

  up to 30th day after surgery

Study Arms (2)

CRT+PD-1 inhibitor+PCSK9 inhibitor

EXPERIMENTAL

Receive long-course radiotherapy in weeks 1-5: 50 Gy/25 f, 2 Gy/day, days 1-5/week; for 5 consecutive weeks; Simultaneously receive 30 days of capetabine treatment at weeks 1-2, weeks 3-5, and weeks 6-8, 825-1000mg/m2, bid, po, days 1-5/week; PD-1 inhibitor: 200mg, iv.gtt, single dose Infusion, a cycle of 21 days, a total of 3 cycles. Carry out at 2 weeks (days 8-14), 5 weeks (days 29-35), and 8 weeks (days 50-56) after the start of radiotherapy; PCSK9 inhibitor: 600 mg, subcutaneous injection, 1, 7 weeks.

Combination Product: Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor

CRT+PD-1 inhibitor

ACTIVE COMPARATOR

Receive long-course radiotherapy in weeks 1-5: 50 Gy/25 f, 2 Gy/day, days 1-5/week; for 5 consecutive weeks; Simultaneously receive 30 days of capetabine treatment at weeks 1-2, weeks 3-5, and weeks 6-8, 825-1000mg/m2, bid, po, days 1-5/week; PD-1 inhibitor: 200mg, iv.gtt, single dose Infusion, a cycle of 21 days, a total of 3 cycles. Carry out at 2 weeks (days 8-14), 5 weeks (days 29-35), and 8 weeks (days 50-56) after the start of radiotherapy.

Combination Product: Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor

Interventions

Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor COMBINATION_PRODUCT

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.

CRT+PD-1 inhibitor

Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor COMBINATION_PRODUCT

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.

CRT+PD-1 inhibitor+PCSK9 inhibitor

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a written informed consent form and voluntarily join this study;
• Age 18-75 years old, male or female;
• Pathologically confirmed adenocarcinoma of the rectum;
• Clinically staged as II\~III stage by MRI (according to the 8th edition of AJCC);
• Tumor lower edge distance from the anal margin ≤10cm;
• Able to undergo surgical resection;
• Able to swallow pills normally;
• ECOG PS 0-1;
• No prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;
• Planning to undergo surgical treatment after completing neoadjuvant therapy;
• No contraindications for surgery;
• Normal major organ function, including:
• 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

You may not qualify if:

• History of allergy to monoclonal antibodies, PD-1 monoclonal antibodies, capecitabine, or oxaliplatin;
• History of receiving or currently receiving any of the following treatments:
• Any surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc., for tumors;
• 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;
• Receipt of attenuated live vaccines within 4 weeks before the first use of the study drug;
• Underwent major surgery or had severe trauma within 4 weeks before the first use of the study drug;
• History of immunodeficiency, including HIV positive, or acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
• 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;
• 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;
• 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;
• 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);
• Pregnant or lactating women;
• 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.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead
• Peking Union Medical College Hospital: collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Changhai Hospital: collaborator

Study Sites (2)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Beijing Friendship Hospital

Beijing, Beijing Municipality, 100050, China

Location

Related Publications (4)

• Liu X, Bao X, Hu M, Chang H, Jiao M, Cheng J, Xie L, Huang Q, Li F, Li CY. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020 Dec;588(7839):693-698. doi: 10.1038/s41586-020-2911-7. Epub 2020 Nov 11.

  PMID: 33177715 BACKGROUND

• Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005 Feb;37(2):161-5. doi: 10.1038/ng1509. Epub 2005 Jan 16.

  PMID: 15654334 BACKGROUND

• Yang Z, Zhang X, Zhang J, Gao J, Bai Z, Deng W, Chen G, An Y, Liu Y, Wei Q, Han J, Li A, Liu G, Sun Y, Kong D, Yao H, Zhang Z. Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial). BMC Cancer. 2022 Apr 27;22(1):462. doi: 10.1186/s12885-022-09554-9.

  PMID: 35477432 BACKGROUND

• Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003 Jun;34(2):154-6. doi: 10.1038/ng1161.

  PMID: 12730697 BACKGROUND

MeSH Terms

Interventions

Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Zhongtao Zhang, MD

CONTACT

+86 13801060364; Zhangzht@ccmu.edu.cn

Hongwei Yao, MD

CONTACT

+8613611015609; yaohongwei@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Experimental: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and PCSK9 inhibitor Control: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: April 1, 2024
• Primary Completion: April 1, 2026
• Study Completion: May 1, 2026
• Last Updated: March 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)