Response to Immunotherapy in MMR-deficient Localized Colon Cancer (RESET-C)

August 12, 2024 updated by: Camilla Qvortrup

Efficacy of Immunotherapy in Patients With MMR-deficient Localized Colon Cancer Scheduled for Curative Surgery - A Prospective, Phase II Study

The aim of this study is to evaluate the safety and efficacy of neoadjuvant treatment with pembrolizumab before colonic resection in patients with early-stage (I-III) deficient mismatch repair (dMMR) colon cancer (CC).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The trial is designed as an investigator-initiated, multicenter, prospective, single arm phase II study in patients with stage I-III dMMR CC scheduled for intended curative surgery to determine the efficacy of immunotherapy using pembrolizumab in the neoadjuvant setting. Patients will receive one dose of pembrolizumab (dosage of 4mg/kg, maximum of 400mg) following diagnosis. After 3 weeks a re-evaluation (to assess tumor response) will be performed, followed by standard surgery for resection of the tumor. Surgery will therefore be performed within 3 to 5 weeks after the dose of pembrolizumab treatment. Following the surgical resection the patients may receive post-operative chemotherapy in accordance with the clinical decision. The patients will be followed as per the standard Danish guidelines with CT scans at 1 and 3 years after surgery.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
85

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Denmark
      • Roskilde, Denmark
        • Zealand University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed localized dMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colon carcinoma.
  2. Indication for elective curative intended surgery without neoadjuvant chemotherapy.
  3. Age of ≥ 18 years.
  4. Written informed consent.
  5. Eastern Cooperative Oncology Group performance status of 0 or 1.

  6. Adequate bone marrow function defined as:

    • Hemoglobin ≥ 6.2 mmol/L or ≥ 10 g/dL.
    • Absolute neutrophil count ≥ 1.5 × 109/L.
    • Platelet count ≥ 100 × 109/L.

  7. Adequate kidney function defined as:

    o Estimated glomerular filtration rate ≥ 60 mL/min or creatinine ≤1.5 × upper limit of normal (ULN).

  8. Adequate liver function defined as:

    • Total bilirubin: ≤ 1.5 × ULN.
    • Alanine aminotransferase: ≤ 2.5 × ULN.
    • Alkaline phosphatase: ≤ 2.5 × ULN.

  9. Follow the conditions regarding fertility, pregnancy, and lactation:

    • Female and male participants of reproductive potential (PORP) must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving pembrolizumab and for 120 days after the dose.
    • PORPs must use, or have their partner use, an acceptable method of contraception e.g. intrauterine device, contraceptive rod implanted into the skin, or hormonal contraceptive and male condom during heterosexual activity, while receiving pembrolizumab and for 120 days after the dose.
    • Women of reproductive potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L HCG) within 72 hours prior to receiving pembrolizumab.
    • Women must not be breastfeeding.

Exclusion Criteria:

  1. Any serious or uncontrolled medical disorder that, in the opinion of the investigator or treating physician, may increase the risk associated with study participation, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  2. Autoimmune disorders (except thyroiditis with replacement therapy and type I diabetes mellitus).
  3. Prior treatment with ICIs or any other antibody/drug specifically targeting the T-cell co-stimulation or checkpoint pathways.
  4. A known history of Human Immunodeficiency Virus, active chronic, or acute Hepatitis B or Hepatitis C.
  5. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  6. Prior participation in another trial with an investigational medicinal product.
  7. Received live vaccines within 30 days prior to pembrolizumab trial treatment. Seasonal influenza vaccines for injection are allowed.
  8. A history of allergy to study drug components or a history of severe hypersensitivity reaction to any monoclonal antibody.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Neoadjuvant pembrolizumab
Pembrolizumab
Drug: Pembrolizumab
One dosage of 4mg/kg (maximum of 400mg)
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR)
Time Frame: Tumour specimen evaluated within 2 weeks after surgery.
Number of patients with pCR evaluated according to the Mandard tumour regression grading system
Tumour specimen evaluated within 2 weeks after surgery.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability of pembrolizumab administered before surgery
Time Frame: Up to approximately 9 weeks
Determined by the incidence and severity of treatment related adverse events according to CTCAE version 5.0
Up to approximately 9 weeks
Postoperative surgical complications
Time Frame: Before and up to 4 weeks after surgery
Number and severity of postoperative surgical complications determined by Clavien-Dindo classification system.
Before and up to 4 weeks after surgery
Immunohistochemistry analysis of markers including CD3, CD8, and PD-L1
Time Frame: Baseline compared to the surgical specimen at 3-5 weeks
Assessment of potential predictive biomarker by investigating immunological markers across pre- and post-treatment biopsies and sequential blood samples.
Baseline compared to the surgical specimen at 3-5 weeks
Methylated circulating cell-free DNA
Time Frame: Up to approximately 9 weeks
Treatment response evaluated by methylated circulating cell-free DNA (cfDNA) specific for CC analysed across sequential blood samples using the TriMeth test
Up to approximately 9 weeks
Gene expression by mRNA
Time Frame: Baseline compared to the surgical specimen at 3-5 weeks
To quantify the expression of genes central to the tumour microenvironment and immune evasion of cancer among others
Baseline compared to the surgical specimen at 3-5 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
TCR sequencing
Time Frame: Baseline compared to 3-5 weeks after pembrolizumab and 2-3 weeks after surgery
To investigate the role of the adaptive immune system in mediating the effect of pembrolizumabrepertoire, CT-scans, endoscopic photo documentation, and patient journals will be analysed with the purpose of identifying biomarkers for predicting pCR.
Baseline compared to 3-5 weeks after pembrolizumab and 2-3 weeks after surgery
CT chest/abdomen scans
Time Frame: 1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab
Evaluated by a multidisciplinary team and centralized comity of radiologists according to the RECIST 1.1 criteria as well as cTNM staging
1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab
Endoscopic tumour assessment
Time Frame: 1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab
Assessed by a systematic approach including the Paris and NICE classifications
1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Camilla Qvortrup

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Odense University Hospital
Zealand University Hospital
Aarhus University Hospital
Bispebjerg Hospital
Vejle Hospital
Aalborg University Hospital
Herlev and Gentofte Hospital
Horsens Hospital
Randers Regional Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ismail Gögenur, Professor, Zealand University Hospital
  • Study Director: Camilla Qvortrup, MD, PhD, Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 22, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 6, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 6, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 22, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 011121

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In accordance with good academic practice, the study data (health data and genomic data) is planned to be transferred in anonymized form to the secure database European Genome-Phenome Archive (EGA). This will happen after the study has been completed. The purpose is to enable sharing of the data with other research groups for future research, inside and outside of Denmark. In all cases, data access decisions will be made by the study protocol committee. Data sharing will be conducted in accordance with the European data protection regulations, including The Danish Data Protection Act and the General Data Protection Regulation. The EGA is part of the European ELIXIR research infrastructure, which is partly funded by the European Commission.

IPD Sharing Time Frame

Planned to begin approximately 6 months end ending approximately 5 years after publication of the final article.

IPD Sharing Access Criteria

Reasonable request. In all cases, data access decisions will be made by the study protocol committee.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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