Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

ctDNA-Guided Immunotherapy for dMMR/MSI-H Colon Cancer

24 de setembro de 2026 atualizado por: Junjie Peng, Fudan University

A Single-Arm Phase II Study of Circulating Tumor DNA-Guided Neoadjuvant Immunotherapy for dMMR/MSI-H Colon Cancer

This prospective, multicenter, single-arm phase II interventional study evaluates whether longitudinal circulating tumor DNA (ctDNA) monitoring can guide neoadjuvant immunotherapy and surgical decision-making in dMMR/MSI-H colon cancer. Participants with ctDNA clearance proceed to curative surgery, whereas those with persistent ctDNA positivity escalate to combined PD-1 and CTLA-4 inhibitor therapy.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This prospective, multicenter, single-arm phase II study evaluates the clinical utility of longitudinal circulating tumor DNA (ctDNA) monitoring to guide neoadjuvant immunotherapy and surgical decision-making in patients with dMMR/MSI-H colon cancer.

Eligible participants will initially receive neoadjuvant PD-1 inhibitor monotherapy. Peripheral-blood ctDNA will be assessed at baseline and after 3 to 4 treatment cycles. Participants with ctDNA clearance will proceed to curative surgery. Participants with persistent ctDNA positivity will be considered to have potential resistance to PD-1 inhibitor monotherapy and will escalate to combined PD-1 and CTLA-4 inhibitor therapy. ctDNA will be reassessed every 2 cycles during combination therapy. Participants will undergo curative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment, regardless of final ctDNA status.

All participants will undergo postoperative ctDNA/minimal residual disease (MRD) testing 1 month after surgery. The study will evaluate pathological response, survival outcomes, the concordance of ctDNA with pathological and imaging assessments, and treatment- and surgery-related safety.

Tipo de estudo

Intervencional

Inscrição (Estimado)

23

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

  • Nome: Junjie Peng, MD, PhD
  • Número de telefone: 86-18017317122
  • E-mail: pengjj@shca.org.cn

Estude backup de contato

Locais de estudo

  • China
      • Shanghai, China, 200000
        • Recrutamento
        • Fudan University Shanghai Cancer Center
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 75 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Written informed consent obtained before any study-related procedures.
  • Age 18 to 75 years, inclusive.
  • Histologically confirmed colon adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma, with the tumor located at least 15 cm from the anal verge.
  • dMMR/MSI-H status confirmed by immunohistochemistry, polymerase chain reaction, or next-generation sequencing.
  • Eastern Cooperative Oncology Group performance status of 0 or 1 and an expected survival of at least 3 months.
  • Adequate hematologic, hepatic, renal, coagulation, thyroid, and cardiac function, as defined in the protocol.
  • Negative pregnancy test for women of childbearing potential; agreement to use highly effective contraception, when applicable.

Exclusion Criteria:

  • Prior treatment with a PD-1 inhibitor, CTLA-4 inhibitor, or other immunotherapy.
  • Symptomatic or high-risk bowel obstruction, bleeding, perforation, pneumonitis, or other conditions that may compromise safe study participation.
  • Another malignancy diagnosed within 5 years before the first study treatment, except for specified definitively treated low-risk malignancies.
  • Current participation in another interventional clinical study, or receipt of another investigational drug or investigational device within 4 weeks before the first study treatment.
  • Active autoimmune disease requiring systemic treatment within 2 years before the first study treatment, or recent systemic corticosteroid or other immunosuppressive therapy.
  • Uncontrolled pleural effusion or ascites, prior allogeneic organ transplantation (except corneal transplantation), or allogeneic hematopoietic stem cell transplantation.
  • Known hypersensitivity to any study drug component.
  • Toxicities or complications from prior treatment not recovered to Grade 1 or baseline, except for specified conditions.
  • HIV infection, untreated active hepatitis B infection, or active hepatitis C infection.
  • Receipt of a live vaccine within 30 days before the first study treatment.
  • Pregnancy or breastfeeding.
  • Any serious or uncontrolled systemic disease, active infection, clinically significant laboratory abnormality, or other condition that may interfere with study participation or place the participant at unacceptable risk, as judged by the investigator.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: ctDNA-Guided Neoadjuvant Immunotherapy |

Participants receive PD-1 inhibitor monotherapy. ctDNA testing after 3-4 cycles determines whether they proceed to curative surgery or escalate to PD-1 plus CTLA-4 inhibitor therapy; all participants subsequently undergo curative surgery.
Medicamento: PD-1 inhibitor

200 mg intravenously on Day 1 of each 3-week cycle. All participants receive initial monotherapy.

Medicamento: CTLA-4 inhibitor

1 mg/kg intravenously on Day 1 of each 3-week cycle. Administered with the PD-1 inhibitor only to participants with persistent ctDNA positivity after 3-4 cycles of monotherapy.

Teste de diagnostico: ctDNA/MRD testing

Peripheral-blood ctDNA testing at baseline and after 3-4 cycles of monotherapy; every 2 cycles during combination therapy, when applicable; and 1 month after surgery.

Procedimento: Curative Surgery

Curative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Pathological Complete Response Rate
Prazo: At curative surgery, following completion of neoadjuvant therapy

Pathological assessment of the surgical resection specimen; pCR is defined as no residual viable cancer cells after treatment (ypT0N0M0).
At curative surgery, following completion of neoadjuvant therapy

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Major Pathological Response Rate
Prazo: At curative surgery, following completion of neoadjuvant therapy

Pathological assessment of the surgical resection specimen; MPR is defined as residual viable tumor cells ≤10%.
At curative surgery, following completion of neoadjuvant therapy
3-Year Event-Free Survival
Prazo: From enrollment up to 3 years

Time from enrollment to first radiographic disease progression or death, whichever occurs first.
From enrollment up to 3 years
3-Year Overall Survival
Prazo: From enrollment up to 3 years

Time from enrollment to death from any cause.
From enrollment up to 3 years
Concordance of ctDNA Status With Pathological Complete Response
Prazo: After 3-4 cycles of PD-1 inhibitor monotherapy (21-day cycles) and at curative surgery; for persistent ctDNA positivity, every 2 cycles of PD-1 plus CTLA-4 inhibitor therapy (21-day cycles; up to 4 cycles).

Preoperative ctDNA status will be compared with postoperative pathological complete response results.
After 3-4 cycles of PD-1 inhibitor monotherapy (21-day cycles) and at curative surgery; for persistent ctDNA positivity, every 2 cycles of PD-1 plus CTLA-4 inhibitor therapy (21-day cycles; up to 4 cycles).
Concordance Between ctDNA Dynamics and Imaging Assessment
Prazo: Baseline through curative surgery, up to 24 weeks (each cycle is 21 days).

ctDNA positivity, clearance, and dynamic changes will be compared with RECIST version 1.1 imaging response assessments.
Baseline through curative surgery, up to 24 weeks (each cycle is 21 days).
Number of Participants With Treatment-Emergent Adverse Events, as Assessed by CTCAE v5.0
Prazo: From first dose through 30 days after the last dose.

Number and proportion of participants with at least one treatment-emergent adverse event, including treatment-related and immune-related adverse events.
From first dose through 30 days after the last dose.
Number of Participants With Grade 3 or Higher Treatment-Related Adverse Events, as Assessed by CTCAE v5.0
Prazo: From first dose through 30 days after the last dose.

Number and proportion of participants with at least one Grade 3 or higher treatment-related adverse event.
From first dose through 30 days after the last dose.
Number of Participants With Serious Adverse Events
Prazo: From first dose through 90 days after the last dose.

Number and proportion of participants with at least one serious adverse event.
From first dose through 90 days after the last dose.
Number of Participants With Treatment-Related Delay of Curative Surgery
Prazo: From first dose through curative surgery up to 24 weeks

Number and proportion of participants whose curative surgery is delayed because of treatment-related toxicity, as determined by the investigator.
From first dose through curative surgery up to 24 weeks

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Fudan University

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

14 de setembro de 2026

Conclusão Primária (Estimado)

31 de dezembro de 2027

Conclusão do estudo (Estimado)

31 de dezembro de 2030

Datas de inscrição no estudo

Enviado pela primeira vez

12 de setembro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

24 de setembro de 2026

Primeira postagem (Real)

25 de setembro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

25 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

24 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • Neo-ctDNA-Colon

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano IPD

Individual participant data, including de-identified data, will not be made available to external researchers. Study data will be processed and stored within China. Aggregate results may be published without identifiable participant information.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever