Research on Effective Strategies After Immunotherapy for Mismatch Repair-deficient Early-stage GI Tumors

A vizsgálat adatai

Ki végzi

University Hospital, Basel, Switzerland

Azonosító

NCT07829081

A regiszteradat frissítve

2026. szeptember 18.

Eredeti leírás

This cohort study is divided into two parts:A teljes eredeti leírásKevesebb

This cohort study is divided into two parts:

Part A: Registry Cohort All patients with non-metastatic, MMRd/MSI-H colorectal cancers (and other gastrointestinal cancers for exploratory analysis) who have signed the general research consent will be included in a prospective registry. This includes patients who undergo primary surgical resection (+/- neoadjuvant/adjuvant therapy) or following immunotherapy, regardless of response.

Part A is a multicenter observational registry with both prospective and retrospective enrolment. Prospective enrolment includes eligible patients entered into the registry after activation of the study at the respective participating site. Retrospective enrolment includes eligible patients diagnosed on or after 1 January 2024 whose clinical data were generated prior to registry activation. Both prospectively and retrospectively enrolled patients contribute to the registry analyses.

Part B: Active Surveillance Cohort (Surveillance Study) A subset of patients from Part A who achieve a complete or near-complete response to ICI therapy, wish to avoid surgery, and are deemed appropriate for non-operative management by a multidisciplinary tumor board are offered inclusion in a phase II surveillance study (Part B). Patients enrolled in Part B will be analysed for the primary endpoint.

Bevonási feltételek: Part A and Part B:; Consent and Capacity:; Participant is 18 years of age or older; Participant is legally competent and able to provide informed consent; Participant has provided the appropriate written consent; Diagnosis: Histologically confirmed gastro-oesophageal, colon or rectum cancer, showing mismatch repair-deficiency (MMRd) by immunohistochemistry (loss of immunoreactivity for at least one of the following proteins: MLH1, PMS2, MSH2 and/or MSH6); Clinical Stage: Non-metastatic, locally advanced disease, defined as:; cT2-T4, cN0-2, cM0 for gastro-oesophageal or rectum cancer; cT4 and/or cN+, cM0 for colon cancer; Therapy with immune checkpoint inhibitor (ICI) as primary treatment, either:; Combination ICI therapy (e.g., anti-PD-1 plus anti-CTLA-4 such as nivolumab + ipilimumab) or; Single-agent ICI therapy (e.g., pembrolizumab, atezolizumab, or other anti- PD(L)1 agents); Part B only:; Patient consents to participate in surveillance study; Complete or near complete response (*) to primary ICI treatment, as determined by local multidisciplinary team (MDT) assessment, based on restaging 8 weeks after termination of the ICI treatment:; Radiological imaging (CT/MRI/PET-CT),; Endoscopic findings, and; Clinical parameters (e.g., normalization of tumor markers, absence of symptoms **); Note: in case of near complete response up to a total of 12 months of ICI is allowed following multidisciplinary team (MDT) discussion. After diagnosis of a near-complete response, tumor reassessments should be performed every 3 months up to a total treatment period of 12 months. If a complete tumor response is observed within the 12-month period, it should be recorded as the best overall response; Note: Assessment of complete or near complete response does not incorporate ctDNA test results.

Kizáró feltételek: Recurrent Disease: Known history of previously treated gastrointestinal cancer with recurrence at time of inclusion; Metastatic Disease: Evidence of distant metastases (M1) at any point prior to or during ICI therapy; Prior Treatment: Any prior systemic therapy, radiotherapy or surgery for the current colon cancer diagnosis before ICI treatment (except biopsy); Other Malignancies: Active second malignancy (excluding non-melanoma skiN cancer or in-situ cervical carcinoma) that may interfere with study outcomes or surveillance; Part B only:; Inadequate response to ICI: Patients with progressive disease, stable disease, or partial response deemed unsuitable for non-operative management; Medical or Psychiatric Conditions: Significant comorbid conditions or psychiatric illness that, in the opinion of the investigator, would impair the patient's ability to comply with protocol requirements, including surveillance; Logistical Barriers: Social, geographic, or organizational factors (e.g., lack of access to regular follow-up care, inability to attend surveillance visits) that would prevent adherence to the active surveillance protocol.

ClinicalTrials.gov NCT07829081