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Registry Study in MSI/dMMR Solid Tumors

Sponsor
Peking University Cancer Hospital & Institute (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06004713
Collaborator
(none)
190
Enrollment
30.1
Anticipated Duration (Months)

Study Details

Study Description

Brief 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. 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.

Condition or Disease Intervention/Treatment Phase

    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.

    Inclusion Criteria:

    • Signing an informed consent form and voluntarily joining this study;

    • Age ≥18 years old; age should also be ≤75 years old in Cohorts B, C, D;

    • Confirmed by histology or cytology as solid malignant tumor and confirmed by immunohistochemistry as dMMR or confirmed by PCR/NGS method as MSI;

    • The researcher determines that the patient can receive anti-tumor treatment;

    • With evaluable lesions.

    Exclusion Criteria:

    • Other malignant tumors within 5 years before enrollment, 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 PSA ≤10 ng/mL at the time of prostate cancer diagnosis (if measured) patients who have undergone radical treatment and have no prostate-specific antigen (PSA) biochemical recurrence can participate in this study), in situ cervical/breast cancer, Lynch syndrome;

    • There is evidence that the patient is a pregnant or lactating woman;

    • Have previously received immunological 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 ICI;

    • The researcher judges other situations that are not suitable for inclusion in the study

    Study endpoints:
    Primary endpoint:

    • The primary endpoint of Cohorts A, B, C, and D are: The progression-free survival (PFS) determined by the researcher according to the RECIST 1.1 standard.

    Secondary endpoints:
    • Efficacy endpoints:

    1. The secondary endpoints for study Cohorts A, B, C, and D include: the overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), and 6-month and 12-month progression-free survival rate of each treatment group; the OS, PFS, ORR, and DCR of each group's post-progression treatment plan; the proportion of each group using ctDNA-guided treatment.

    2. In Cohort A, the OS, PFS, ORR, DCR, DOR, TTR, 6-month and 12-month progression-free survival rate of Group A1 (ctDNA detection/intervention group) and Group A2 (ctDNA detection/non-intervention group).

    3. In patients with long-term disease control under ICIs treatment: the proportion of patients who are MRD-negative after one year, patients who are MRD-negative and stopped medication after one year, patients who are MRD-positive after one year, and patients who are MRD-positive and stopped medication after one year, as well as their OS, PFS, ORR, DCR, 6-month and 12-month progression-free survival rate.

    4. In patients resistant to ICIs treatment: the proportion of patients who retested tissue or blood genes at progression, as well as the proportion of patients who adjusted treatment plans based on gene testing and their OS, PFS, ORR, DCR, 6-month and 12-month progression-free survival rate.

    5. The proportion of patients using ctDNA-guided treatment and not using ctDNA-guided treatment, as well as their OS, PFS, ORR, DCR, 6-month and 12-month progression-free survival rate.

    6. Among each group: patients who are often excluded from clinical trials: their OS, PFS, ORR, DCR, DOR, TTR, 6-month and 12-month progression-free survival rate

    • Safety endpoints (Cohort A, B, C, D): incidence of adverse events (AE) during treatment, AE-related discontinuation rate, AE relief rate

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    190 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability
    Anticipated Study Start Date :
    Aug 1, 2023
    Anticipated Primary Completion Date :
    Feb 1, 2026
    Anticipated Study Completion Date :
    Feb 1, 2026

    Arms and Interventions

    Arm Intervention/Treatment
    Cohort A

    Patients will initially receive monotherapy PD1/PDL1 monoclonal antibody therapy.
    Cohort B

    Patients will initially receive dual blockade of both PD1/PDL1 and CTLA4
    Cohort C

    Patients will initially receive PD1/PDL1 monoclonal antibody combined with chemotherapy or targeted therapy.
    Cohort D

    Patients will receive other standard treatments for this tumor other than ICIs.

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) determined by the researchers according to the RECIST 1.1 criteria.. [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

      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.

    Secondary Outcome Measures

    1. Overall survival [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

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

    2. Overall response rate [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

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

    3. Disease control rate [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

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

    4. Duration of response [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose]

      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.

    5. Treatment-related adverse event [Informed consent to 30 days after last dose of treatment]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Peking University Cancer Hospital & Institute

    Investigators

    • Study Director: zhenghang Wang, Peking University Cancer Hospital & Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Peking University Cancer Hospital & Institute
    ClinicalTrials.gov Identifier:
    NCT06004713
    Other Study ID Numbers:
    • LGH2023093
    First Posted:
    Aug 22, 2023
    Last Update Posted:
    Aug 22, 2023
    Last Verified:
    Jul 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Aug 22, 2023