Quality of Life (QOL)RESISTNCT07829081
Research on Effective Strategies After Immunotherapy for Mismatch Repair-deficient Early-stage GI Tumors
An observational study of Quality of Life (QOL) and Mismatch Repair Deficient Colorectal Cancer, run by University Hospital, Basel, Switzerland at 3 sites in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Quality of Life (QOL), Mismatch Repair Deficient Colorectal Cancer, Microsatellite Instability-High Colorectal Cancer
- What is being tested?
- Active surveillance after complete response to immunotherapy in MMRd GI cancers and Stand of Care
- How many people
- 234 participants
- Where
- 3 sitesSwitzerland
- Study dates
- 1 Sep 2026to 31 Aug 2033
- Phase
- Observational
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 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.
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
- Part B only:
- Inadequate response to ICI: Patients with progressive disease, stable disease, or partial response deemed unsuitable for non-operative management.
- Prior Treatment: Any prior systemic therapy, radiotherapy or surgery for the current colon cancer diagnosis before ICI treatment (except biopsy)
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland3 sites, 3 recruiting
- Recruiting
Universitätsspital Basel
Basel, 4031
Viviane Hess, Prof. Dr. med., +41 61 265 50 59, viviane.hess@usb.ch
- Recruiting
Spitalzentrum Biel
Biel, 2501
Carsten Viehl, Prof. Dr. med., +41 32 324 37 64, carsten.viehl@szb-chb.ch
- Recruiting
Luzerner Kantonsspital
Lucerne, 6000
Jörn Markus Gass, PD Dr. med., +41 41 205 45 39, markus.gass@luks.ch
About this study
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.
Read more
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.
Read the detailed description
Background and Rationale: Mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers represent a distinct molecular subtype characterized by high tumor mutational burden and increased immunogenicity. Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in this population, with recent studies showing high rates of pathological complete response (pCR) when used in the neoadjuvant setting for non-metastatic GI cancers and colorectal cancers in particular. These results raise important questions about the necessity of surgical resection in patients who achieve complete clinical response (cCR) after ICI therapy.
Avoiding surgery in patients with complete response through an active surveillance approach could significantly reduce treatment-related morbidity and improve quality of life for selected patients. However, this strategy remains investigational and robust clinical evidence is lacking regarding its safety, long-term oncologic outcomes and appropriate selection criteria. Our study seeks to address this gap by evaluating response-guided, non-operative management in patients with non-metastatic MMRd/ MSI-H GI tumors treated primarily with immunotherapy.
Objectives: The primary objective of this study is to evaluate 2-year relapse-free survival (RFS) in patients with non-metastatic, mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) in patients with stage II/III colorectal cancer who achieve a complete or near-complete response following primary treatment with immune checkpoint inhibitors (ICIs) who enter Part B of the study (surveillance study).
Method: 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. Treatment regimens include PD-(L)1 monotherapy (e.g., pembrolizumab, atezolizumab) or combination ICI therapy (e.g., nivolumab plus ipilimumab), administered at the discretion of the treating oncologist for up to 6 months (in case of near complete response ICI may be continued up to a total of 12 months following multidisciplinary evaluation).
Patients who do not achieve a complete or near-complete clinical response-or who are not eligible or not willing to undergo non-operative management-proceed to standard oncological surgery (with or without neo-/adjuvant systemic therapy), in accordance with clinical guidelines. Postoperatively, they receive routine oncological follow-up per institutional standards and remain in registry cohort (Part A).
Patients who demonstrate a complete or near-complete clinical response to ICI and are considered eligible for non-surgical management (based on multidisciplinary evaluation), enter an intensified surveillance program in lieu of immediate surgery (Part B).
The active surveillance includes Clinical assessments, Cross-sectional imaging (e.g., CT or MRI) , Endoscopic evaluations at defined intervals and Facultative ctDNA testing 6 months after completion of immunotherapy (Part B)
- Conditions
- Quality of Life (QOL), Mismatch Repair Deficient Colorectal Cancer, Microsatellite Instability-High Colorectal Cancer, Stage II Colorectal Cancer, Stage III Colorectal Cancer, Mismatch Repair- Deficient Rectal Cancer
- Being tested
- Active surveillance after complete response to immunotherapy in MMRd GI cancers, Stand of Care
- Keywords
- Mismatch Repair Deficiency, Active Surveillance, Microsatellite High, Microsatellite instability-high, MMRd colorectal cancer, MSI-H colorectal cancer, MSI-H gastric cancer, Stage II colorectal cancer, Stage III colorectal cancer, Immune checkpoint inhibitor, ICI therapy, PD-1 inhibitor, PD-L1 inhibitor, Combination immunotherapy, Complete clinical response, Near-complete response, Pathological complete response, Non-operative management, Watch-and-wait, Surveillance cohort
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active surveillance after complete response to immunotherapy in MMRd GI cancersOther
Also called watch and wait
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 CareOther
Patients in the Standard of care Arm (Arm A) will receive a resection of the primary tumour after completion of the immunecheckpoint inhibition therapy.
| Study group | Role | What they receive |
|---|---|---|
| Active Surveillance after ICI response instead of surgery | Participants with mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) stage II/III gastrointestinal cancer who achieve a complete or near-complete response after immune checkpoint inhibitor (ICI) therapy enter a structured active surveillance program instead of undergoing immediate surgery. Surveillance includes scheduled radiologic imaging, endoscopic evaluation, clinical assessment, and biomarker monitoring to detect relapse early and allow timely salvage treatment. Receives: Other: Active surveillance after complete response to immunotherapy in MMRd GI cancers | |
| Standard of Care Cohort | Patients that receive an operation to remove the primary tumour after completion of immunecheckpoint therapy for MSI high colorectal cancer (resp. other MSI high GI cancer). Receives: Other: Stand of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (2)
Relapse-Free Survival - other GI Cancers
applied to patients with non-metastatic MMRd/MSI-H gastroesophageal or other GI cancers entering active surveillance.
Measured: 24 months
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study start1 Sep 2026
- Primary completion31 Aug 2033 (estimated)
- Study completion31 Aug 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Quality of Life (QOL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 234 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07829081
- Sponsor's protocol ID
- RESIST
- Acronym
- RESIST
- Status last verified
- Sep 2026
- First submitted
- 14 Sep 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No