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DMMR CancerNCT06004713

Registry Study in MSI/dMMR Solid Tumors

An observational study of DMMR Cancer and MSI-H, run by Peking University Cancer Hospital & Institute at 10 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 The sponsor has not verified this record for over two years, so it may be out of date.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 study is a multi-center, non-interventional, prospective clinical observational study, aiming to evaluate the effectiveness and safety of subsequent treatment in dMMR/MSI solid tumor patients who have never received ICIs under real-world conditions. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
DMMR Cancer, MSI-H, Solid Tumor
How many people
190 participants
Where
10 sitesChina
Study dates
7 Oct 2023to Feb 2026
Phase
Observational
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The estimated start time of this study is August 2023, and data will be collected from enrolled patients nationwide over a period of 3 years. It is planned to enroll 100 patients in Cohort A, including 25 in Group A1 and 25 in Group A2. It is planned to enroll 30 patients in Cohort B, 30 in Cohort C, and 30 in Cohort D.

Who may be able to join

  • Sign the informed consent form and voluntarily participate in this study;
  • Age ≥ 18 years old; age should also be ≤75 years old in Cohorts B, C, D;
  • Histologically or cytologically confirmed to have a solid malignant tumor and confirmed by immunohistochemistry to be dMMR or confirmed by PCR/NGS to be MSI;
  • The researcher determines that the patient can receive anti-tumor treatment;
  • Have evaluable lesions

Who cannot join

  • Other malignant tumors within 5 years before joining the study, except for cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle invasive bladder cancer, localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6 points, and prostate cancer diagnosed with PSA ≤10 ng/mL (if measured). Patients who have received radical treatment and have no prostate specific antigen (PSA) biochemical recurrence can participate in this study), cervical/breast carcinoma in situ, and Lynch syndrome;
  • Evidence already exists that the patient is a pregnant or lactating woman;
  • Previous treatment with immune checkpoint inhibitors or T cell co-stimulatory drugs, including but not limited to PD1, CTLA4, LAG3, and other immune checkpoint blockers, therapeutic vaccines, etc.; patients exposed to ICIs in perioperative setting are allowed to be enrolled if disease relapse after more than 6 months since the last dose of ICIs;
  • Other situations deemed by the researcher to be unsuitable for inclusion in the study

Trial locations and contacts

10 sites in 1 country.

zhenghang Wang contact

18813186790

zhenghang_wang@bjmu.edu.cn

10 sites in 1 country

China10 sites, 10 recruiting

  • Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute

    Beijin, Beijing Municipality, 100142

    Zhenghang Wang

    Recruiting

  • Department of Medical Oncology, Peking University First Hospital

    Beijing

    Xuan Jin

    Recruiting

  • Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University

    Beijing

    Dong Yan

    Recruiting

  • Department of Oncology, Peking University Shougang Hospital

    Beijing

    Xiaodong Wang

    Recruiting

  • Department of Oncology, The Affiliated Hospital of Qingdao University

    Qingdao, Shandong

    Zimin Liu

    Recruiting

  • Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute

    Shengyang, Liaoning

    Qiwei Wang

    Recruiting

  • Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei

    Fengbin Zhang

    Recruiting

  • Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital

    Taiyuan, Shanxi

    Hongxia Lu

    Recruiting

  • Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital

    Tianjin

    Ting Deng

    Recruiting

  • Department of Oncology, The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan

    Zhiwei Chang

    Recruiting

Other trials in China

About this study

Official title: Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability

This study is a multi-center, non-interventional, prospective clinical observational study, aiming to evaluate the effectiveness and safety of subsequent treatment in dMMR/MSI solid tumor patients who have never received ICIs under real-world conditions. Particular attention is paid to the efficacy in populations where treatment plans are adjusted based on ctDNA, and potential predictive or prognostic biomarkers are explored.

Read the detailed description

This study plans to enroll patients in the following four cohorts:

  • Cohort A: Initially only receiving PD1/PDL1 monotherapy;
  • Cohort B: Initially receiving simultaneous blockade of PD1/PDL1 and CTLA4;
  • Cohort C: Initially receiving PD1/PDL1 monotherapy combined with chemotherapy or targeted therapy;
  • Cohort D: Initially not using ICIs, receiving other standard treatments for this tumor type

To explore the role of ctDNA testing in therapeutic decision-making, patients with the first evaluation of SD in cohort A are divided into two groups: ctDNA testing/intervention group (Group A1) and ctDNA testing/non-intervention group (Group A2). In group A1, if there is no early response to ctDNA, the researchers and the patient will decide to add CTLA4 antibody or other potentially effective treatments after thorough communication. If there is an early response to ctDNA, then continue with PD1/PDL1 monoclonal antibody treatment. Patients in group A2 undergo ctDNA testing, but still continue with PD1/PDL1 monoclonal antibody treatment according to the RECIST v1.1 standard when the first evaluation of SD is made. Meanwhile, explore the role of 1-year ctDNA-MRD in guiding treatment in patients with long-term tumor control, and explore the guiding role of re-biopsy of tumor tissue or ctDNA testing in helping making treatment regimen after progression on ICIs.

Number of Subjects:

  • This study will recruit patients nationwide for data collection over a period of 3 years. The plan is to enroll 100 cases in Cohort A, including 25 cases in Group A1 and 25 cases in Group A2; 30 cases in Cohort B; 30 cases in Cohort C; and 30 cases in Cohort D.

What participants receive

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

Study groups in NCT06004713
Study groupRoleWhat they receive
Cohort APatients will initially receive monotherapy PD1/PDL1 monoclonal antibody therapy.
Cohort BPatients will initially receive dual blockade of both PD1/PDL1 and CTLA4
Cohort CPatients will initially receive PD1/PDL1 monoclonal antibody combined with chemotherapy or targeted therapy.
Cohort DPatients will receive other standard treatments for this tumor other than ICIs.

What is being measured

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

  1. Progression-free survival (PFS) determined by the researchers according to the RECIST 1.1 criteria..

    Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.

    Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose

Secondary outcomes (5)

  1. Overall survival

    Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.

    Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose

  2. Overall response rate

    Objective response rate (defined as CR+PR) will be reported based on investigator's evaluation.

    Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose

  3. Disease control rate

    Disease control rate (defined as CR+PR+SD) will be reported based on investigator's evaluation.

    Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose

  4. Duration of response

    Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause.

    Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose

  5. Treatment-related adverse event

    A treatment-related adverse event (TRAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TRAEs were graded using National Cancer Institute (NCI)-CTCAE version 5.0.

    Measured: Informed consent to 30 days after last dose of treatment

Timeline

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

  1. First posted22 Aug 2023
  2. Study start7 Oct 2023
  3. Primary completionFeb 2026 (estimated)
  4. Study completionFeb 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
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
190 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06004713
Sponsor's protocol ID
LGH2023093
Status last verified
Jul 2023
First submitted
16 Aug 2023
Last updated
25 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F, Scarpa A. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019 Aug 1;30(8):1232-1243. doi: 10.1093/annonc/mdz116.

    PubMed 31056702

  • Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

    PubMed 28596308

  • Wang Z, Zhao X, Gao C, Gong J, Wang X, Gao J, Li Z, Wang J, Yang B, Wang L, Zhang B, Zhou Y, Wang D, Li X, Bai Y, Li J, Shen L. Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment. J Immunother Cancer. 2020 Nov;8(2):e001297. doi: 10.1136/jitc-2020-001297.

    PubMed 33172882

  • Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699.

    PubMed 33264544

  • Zhu M, Jin Z, Hubbard JM. Management of Non-Colorectal Digestive Cancers with Microsatellite Instability. Cancers (Basel). 2021 Feb 6;13(4):651. doi: 10.3390/cancers13040651.

    PubMed 33561950

  • Chida K, Kawazoe A, Kawazu M, Suzuki T, Nakamura Y, Nakatsura T, Kuwata T, Ueno T, Kuboki Y, Kotani D, Kojima T, Taniguchi H, Mano H, Ikeda M, Shitara K, Endo I, Yoshino T. A Low Tumor Mutational Burden and PTEN Mutations Are Predictors of a Negative Response to PD-1 Blockade in MSI-H/dMMR Gastrointestinal Tumors. Clin Cancer Res. 2021 Jul 1;27(13):3714-3724. doi: 10.1158/1078-0432.CCR-21-0401. Epub 2021 Apr 29.

    PubMed 33926917

  • Wang Z, Wang X, Xu Y, Li J, Zhang X, Peng Z, Hu Y, Zhao X, Dong K, Zhang B, Gao C, Zhao X, Chen H, Cai J, Bai Y, Sun Y, Shen L. Mutations of PI3K-AKT-mTOR pathway as predictors for immune cell infiltration and immunotherapy efficacy in dMMR/MSI-H gastric adenocarcinoma. BMC Med. 2022 Apr 21;20(1):133. doi: 10.1186/s12916-022-02327-y.

    PubMed 35443723

  • Wang Z, Zhang Q, Qi C, Bai Y, Zhao F, Chen H, Li Z, Wang X, Chen M, Gong J, Peng Z, Zhang X, Cai J, Chen S, Zhao X, Shen L, Li J. Combination of AKT1 and CDH1 mutations predicts primary resistance to immunotherapy in dMMR/MSI-H gastrointestinal cancer. J Immunother Cancer. 2022 Jun;10(6):e004703. doi: 10.1136/jitc-2022-004703.

    PubMed 35705314

  • Malla M, Loree JM, Kasi PM, Parikh AR. Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices. J Clin Oncol. 2022 Aug 20;40(24):2846-2857. doi: 10.1200/JCO.21.02615. Epub 2022 Jul 15.

    PubMed 35839443

  • Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W, Abdullah SE, Higgs BW, Dennis PA, van der Heijden MS, Segal NH, Chaft JE, Hembrough T, Barrett JC, Hellmann MD. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020 Dec;10(12):1842-1853. doi: 10.1158/2159-8290.CD-20-0047. Epub 2020 Aug 14.

    PubMed 32816849

  • Kasi PM, Budde G, Krainock M, Aushev VN, Koyen Malashevich A, Malhotra M, Olshan P, Billings PR, Aleshin A. Circulating tumor DNA (ctDNA) serial analysis during progression on PD-1 blockade and later CTLA-4 rescue in patients with mismatch repair deficient metastatic colorectal cancer. J Immunother Cancer. 2022 Jan;10(1):e003312. doi: 10.1136/jitc-2021-003312.

    PubMed 35101943

  • Luo J, Wu S, Rizvi H, Zhang Q, Egger JV, Osorio JC, Schoenfeld AJ, Plodkowski AJ, Ginsberg MS, Callahan MK, Maher C, Shoushtari AN, Postow MA, Voss MH, Kotecha RR, Gupta A, Raja R, Kris MG, Hellmann MD. Deciphering radiological stable disease to immune checkpoint inhibitors. Ann Oncol. 2022 Aug;33(8):824-835. doi: 10.1016/j.annonc.2022.04.450. Epub 2022 May 6.

    PubMed 35533926

  • Bui QL, Mas L, Hollebecque A, Tougeron D, de la Fouchardiere C, Pudlarz T, Alouani E, Guimbaud R, Taieb J, Andre T, Colle R, Cohen R. Treatments after Immune Checkpoint Inhibitors in Patients with dMMR/MSI Metastatic Colorectal Cancer. Cancers (Basel). 2022 Jan 14;14(2):406. doi: 10.3390/cancers14020406.

    PubMed 35053568

  • Hollebecque A, Chung HC, de Miguel MJ, Italiano A, Machiels JP, Lin CC, Dhani NC, Peeters M, Moreno V, Su WC, Chow KH, Galvao VR, Carlsen M, Yu D, Szpurka AM, Zhao Y, Schmidt SL, Gandhi L, Xu X, Bang YJ. Safety and Antitumor Activity of alpha-PD-L1 Antibody as Monotherapy or in Combination with alpha-TIM-3 Antibody in Patients with Microsatellite Instability-High/Mismatch Repair-Deficient Tumors. Clin Cancer Res. 2021 Dec 1;27(23):6393-6404. doi: 10.1158/1078-0432.CCR-21-0261. Epub 2021 Aug 31.

    PubMed 34465599

  • Chen M, Wang Z, Liu Z, Liu N, Fang W, Zhang H, Jin X, Li J, Zhao W, Qu H, Song F, Chang Z, Li Y, Tang Y, Xu C, Zhang X, Wang X, Peng Z, Cai J, Li J, Shen L. The Optimal Therapy after Progression on Immune Checkpoint Inhibitors in MSI Metastatic Gastrointestinal Cancer Patients: A Multicenter Retrospective Cohort Study. Cancers (Basel). 2022 Oct 21;14(20):5158. doi: 10.3390/cancers14205158.

    PubMed 36291942

Questions about this trial

What is this clinical trial studying?

An observational study of DMMR Cancer and MSI-H, run by Peking University Cancer Hospital & Institute at 10 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 5 inclusion and 4 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 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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.

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 zhenghang Wang (18813186790, zhenghang_wang@bjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) determined by the researchers according to the RECIST 1.1 criteria.. (time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose). 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 NCT06004713, which also lists 15 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 25 Oct 2023.

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