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

ConditionsQuality of Life (QOL)Mismatch Repair Deficient Colorectal CancerMicrosatellite Instability-High Colorectal CancerStage II Colorectal CancerStage III Colorectal CancerMismatch Repair- Deficient Rectal CancerMicrosatellite Instability-High Rectal CancerMismatch Repair-Deficient Colon CancerMismatch Repair-Deficient Gastroesophageal AdenocarcinomaMicrosatellite Instability-High Gastroesophageal AdenocarcinomaMismatch Repair-Deficient Gastric Cancer
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity Hospital, Basel, Switzerland

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Other Malignancies: Active second malignancy (excluding non-melanoma skiN cancer or in-situ cervical carcinoma) that may interfere with study outcomes or surveillance.

Inadequate response to ICI: Patients with progressive disease, stable disease, or partial response deemed unsuitable for non-operative management.

Trial population

The study population includes adult patients with non-metastatic MSI-H/MMRd gastrointestinal cancers, specifically colorectal (colon and rectal) cancer as well as gastro-oesophageal and gastric adenocarcinoma. Eligible participants must have achieved a complete or near-complete clinical response following immune checkpoint inhibitor therapy, with no radiologic, endoscopic, or histologic evidence of residual disease at the time of response assessment. Patients are enrolled into a structured active surveillance program instead of undergoing immediate surgical resection. Individuals with metastatic disease, insufficient response to immunotherapy or contraindications to surveillance procedures are excluded.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Active surveillance after complete response to immunotherapy in MMRd GI cancers

    Other intervention

    Eligible patients may receive immune checkpoint inhibitor (ICI) therapy as the primary treatment for mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H), locally advanced, non-metastatic gastrointestinal cancer according to local practice. In case of near complete response ICI may be continued up to a total of 12 months following multidisciplinary evaluation. Part A includes all patients with stage II or III colorectal cancer (esophageal adenocarcinoma, gastric cancer will be allowed as well) confirmed as MMRd/MSI-H. Patients are enrolled regardless of treatment strategy, including those receiving immune checkpoint inhibitor (ICI) therapy or primary surgery. 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 active surveillance protocol (Part B).

  • Stand of Care

    Other intervention

    Patients in the Standard of care Arm (Arm A) will receive a resection of the primary tumour after completion of the immunecheckpoint inhibition therapy.

Treatment groups

234 Participants
are divided into 2 treatment groups
Group A: Active Surveillance after ICI response instead of surgery1 intervention
Group B: Standard of Care Cohort1 intervention

Trial outcomes

Primary outcomes

1

Relapse-Free Survival (RFS)

The proportion of patients with colorectal cancers who remain free from local, regional, or distant recurrence at 24 months after achieving a complete or near-complete clinical response to immune checkpoint inhibitor therapy and undergoing active surveillance. Recurrence is defined as radiologic, endoscopic, or histologic evidence of tumor regrowth requiring salvage surgery or systemic treatment.

Time frame
24 months

Secondary outcomes

1

Relapse-Free Survival - other GI Cancers

applied to patients with non-metastatic MMRd/MSI-H gastroesophageal or other GI cancers entering active surveillance.

Time frame
24 months
2

Clinical Complete Response (cCR) Rate

Proportion of patients achieving clinical complete response, near-complete response, partial response, stable disease, or progressive disease following ICI therapy, assessed by radiologic, endoscopic, clinical criteria, and biopsy results.

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Hospital, Basel, Switzerland

Lead sponsor

Source ClinicalTrials.gov
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