Response to Immunotherapy in MMR-deficient Localized Colon Cancer
RESET-C
Efficacy of Immunotherapy in Patients With MMR-deficient Localized Colon Cancer Scheduled for Curative Surgery - A Prospective, Phase II Study
1 other identifier
interventional
85
1 country
1
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2023
Shorter than P25 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 24, 2022
CompletedFirst Posted
Study publicly available on registry
December 22, 2022
CompletedStudy Start
First participant enrolled
February 22, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 6, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 6, 2024
CompletedAugust 13, 2024
August 1, 2024
1.3 years
November 24, 2022
August 12, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Pathological complete response (pCR)
Number of patients with pCR evaluated according to the Mandard tumour regression grading system
Tumour specimen evaluated within 2 weeks after surgery.
Secondary Outcomes (5)
Safety and tolerability of pembrolizumab administered before surgery
Up to approximately 9 weeks
Postoperative surgical complications
Before and up to 4 weeks after surgery
Immunohistochemistry analysis of markers including CD3, CD8, and PD-L1
Baseline compared to the surgical specimen at 3-5 weeks
Methylated circulating cell-free DNA
Up to approximately 9 weeks
Gene expression by mRNA
Baseline compared to the surgical specimen at 3-5 weeks
Other Outcomes (3)
TCR sequencing
Baseline compared to 3-5 weeks after pembrolizumab and 2-3 weeks after surgery
CT chest/abdomen scans
1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab
Endoscopic tumour assessment
1-5 weeks before pembrolizumab and 3-5 weeks after pembrolizumab
Study Arms (1)
Neoadjuvant pembrolizumab
EXPERIMENTALPembrolizumab
Interventions
One dosage of 4mg/kg (maximum of 400mg)
Eligibility Criteria
You may qualify if:
- Histologically confirmed localized dMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colon carcinoma.
- Indication for elective curative intended surgery without neoadjuvant chemotherapy.
- Age of ≥ 18 years.
- Written informed consent.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- 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.
- Adequate kidney function defined as:
- o Estimated glomerular filtration rate ≥ 60 mL/min or creatinine ≤1.5 × upper limit of normal (ULN).
- Adequate liver function defined as:
- Total bilirubin: ≤ 1.5 × ULN.
- Alanine aminotransferase: ≤ 2.5 × ULN.
- Alkaline phosphatase: ≤ 2.5 × ULN.
- +5 more criteria
You may not qualify if:
- 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.
- Autoimmune disorders (except thyroiditis with replacement therapy and type I diabetes mellitus).
- Prior treatment with ICIs or any other antibody/drug specifically targeting the T-cell co-stimulation or checkpoint pathways.
- A known history of Human Immunodeficiency Virus, active chronic, or acute Hepatitis B or Hepatitis C.
- 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.
- Prior participation in another trial with an investigational medicinal product.
- Received live vaccines within 30 days prior to pembrolizumab trial treatment. Seasonal influenza vaccines for injection are allowed.
- A history of allergy to study drug components or a history of severe hypersensitivity reaction to any monoclonal antibody.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Camilla Qvortruplead
- Zealand University Hospitalcollaborator
- Odense University Hospitalcollaborator
- Vejle Hospitalcollaborator
- Herlev and Gentofte Hospitalcollaborator
- Bispebjerg Hospitalcollaborator
- Aalborg University Hospitalcollaborator
- Horsens Hospitalcollaborator
- Randers Regional Hospitalcollaborator
- Aarhus University Hospitalcollaborator
Study Sites (1)
Zealand University Hospital
Roskilde, Denmark
Related Publications (2)
Gogenur I, Justesen TF, Tarpgaard LS, Bulut M, Hansen TF, Jensen LH, Rahr HB, Kirkegaard T, Balsevicius L, Raskov H, Petersen PC, Eriksen JR, Salomon S, Fiehn AK, Brandsborg S, Gotschalck KA, Emmertsen KJ, Born PW, Thorlacius-Ussing O, Lauritzen MB, Olesen RK, Poulsen LO, Lykke J, Schou J, Buskov L, Krarup PM, Andersen CL, Pfeiffer P, Qvortrup C. Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial. Ann Surg. 2024 Dec 18. doi: 10.1097/SLA.0000000000006611. Online ahead of print.
PMID: 39692004DERIVEDJustesen TF, Gogenur I, Tarpgaard LS, Pfeiffer P, Qvortrup C. Evaluating the efficacy and safety of neoadjuvant pembrolizumab in patients with stage I-III MMR-deficient colon cancer: a national, multicentre, prospective, single-arm, phase II study protocol. BMJ Open. 2023 Jun 22;13(6):e073372. doi: 10.1136/bmjopen-2023-073372.
PMID: 37349100DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Camilla Qvortrup, MD, PhD
Rigshospitalet, Denmark
- PRINCIPAL INVESTIGATOR
Ismail Gögenur, Professor
Zealand University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Senior physician oncology
Study Record Dates
First Submitted
November 24, 2022
First Posted
December 22, 2022
Study Start
February 22, 2023
Primary Completion
June 6, 2024
Study Completion
June 6, 2024
Last Updated
August 13, 2024
Record last verified: 2024-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Planned to begin approximately 6 months end ending approximately 5 years after publication of the final article.
- Access Criteria
- Reasonable request. In all cases, data access decisions will be made by the study protocol committee.
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.