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Locally Advanced Rectal CancerPhase 2NCT06304987

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

A Phase 2 study testing Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor and Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor in people with Locally Advanced Rectal Cancer, run by Beijing Friendship Hospital at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Locally Advanced Rectal Cancer
What is being tested?
Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor and Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesChina
Study dates
Apr 2024to May 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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
  • Hemoglobin ≥90 g/L
  • 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)
  • 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.

Who cannot join

  • 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;
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  • 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;
  • 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);
  • 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;
  • 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.

Trial locations and contacts

2 sites in 1 country.

Zhongtao Zhang, MD contact

+86 13801060364

Zhangzht@ccmu.edu.cn

China2 sites
  • Beijing Friendship Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100050

  • Beijing Friendship Hospital

    Beijing, Beijing Municipality, 100050

Other trials in China

About this study

Official title: The Efficacy and Safety of Preoperative Neoadjuvant Chemoradiation Combined With PD-1 Inhibitor and PCSK9 Inhibitor in the Treatment of pMMR/MSS Locally Advanced Middle and Low Rectal Cancer: a Multicenter Study, Prospective, Randomized Controlled Study

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.

Read the 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.

Being tested
Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor, Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor
Keywords
pMMR/MSS, PD-1, PCSK9, chemoradiation, neoadjuvant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitorCombination 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.

  • Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitorCombination 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.

Study groups in NCT06304987
Study groupRoleWhat they receive
CRT+PD-1 inhibitor+PCSK9 inhibitorExperimentalReceive 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.
Receives: Combination Product: Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor
CRT+PD-1 inhibitorActive comparatorReceive 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.
Receives: Combination Product: Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CR

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

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

  2. AE rate

    Adverse event rate

    Measured: during treatment

Secondary outcomes (4)
  1. NAR score

    Neoadjuvant rectal(NAR)score:It is based on the scoring criteria of preoperative treatment

    Measured: within 10 days after surgery

  2. OPR

    organ preservation rate

    Measured: immediately after surgery

  3. ORR

    objective response rate

    Measured: within 10 days after surgery

  4. immune-related adverse event rate

    adverse event rate that is deemed to be associated with PD-1 inhibition

    Measured: up to 30th day after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2024
  2. Study startApr 2024 (estimated)
  3. Primary completionApr 2026 (estimated)
  4. Study completionMay 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Experimental: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and PCSK9 inhibitor Control: Neoadjuvant chemoradiotherapy combined with PD-1 inhibitor
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06304987
Sponsor's protocol ID
BFH-niCRT-05
Status last verified
Mar 2024
First submitted
5 Mar 2024
Last updated
19 Mar 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Export of individual patient data is a sensitive issue according to current Chinese laws.

Publications

  • 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.

    PubMed 33177715
  • 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.

    PubMed 15654334
  • 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.

    PubMed 35477432
  • 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.

    PubMed 12730697

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Long-course chemoradiation and PD-1 inhibitor, with PCSK9 inhibitor and Long-course chemoradiation and PD-1 inhibitor, without PCSK9 inhibitor in people with Locally Advanced Rectal Cancer, run by Beijing Friendship Hospital at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Zhongtao Zhang, MD (+86 13801060364, Zhangzht@ccmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CR (time frame: pCR :within 10 days after surgery;cCR :12-13 weeks after radiotherapy ends). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06304987, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.

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