Clinical trial NCT06004713: Registry Study in MSI/dMMR Solid Tumors
Official title: Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: DMMR Cancer
MSI-H
Solid Tumor
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2023-08-22
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS) determined by the researchers according to the RECIST 1.1 criteria..
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Secondary outcomes:
measure: Overall survival
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Overall response rate
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Disease control rate
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Duration of response
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
measure: Treatment-related adverse event
timeFrame: Informed consent to 30 days after last dose of treatment
Other outcomes:
Locations:
city: Beijin
country: China
facility: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute
state: Beijing
city: Shijiazhuang
country: China
facility: Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Department of Oncology, The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Shengyang
country: China
facility: Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute
state: Liaoning
city: Qingdao
country: China
facility: Department of Oncology, The Affiliated Hospital of Qingdao University
state: Shandong
city: Taiyuan
country: China
facility: Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital
state: Shanxi
city: Beijing
country: China
facility: Department of Medical Oncology, Peking University First Hospital
city: Beijing
country: China
facility: Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University
city: Beijing
country: China
facility: Department of Oncology, Peking University Shougang Hospital
city: Tianjin
country: China
facility: Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: zhenghang Wang
role: STUDY_DIRECTOR
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