NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer

Sponsor
University College, London
Study ID
NCT05197322
Phase
PHASE2
Status
Recruiting
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Conditions

  • Adenocarcinoma of the Colon

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — DRUG
    Dose: 200mg by IV infusion on Day 1 of each treatment cycle
  • Pembrolizumab — DRUG
    Dose: 200mg by IV infusion on Day 1 of Cycle 1 only

Study Details

Colorectal cancer (CRC) is the 2nd to 3rd most common malignant disease in developed countries, with over 1 million new cases and 500,000 deaths worldwide each year. The primary treatment for early stage CRC is surgery to remove the tumour, which is possible in 80% of patients. Even after surgery up to half of patients will develop recurrence or spread of the disease (metastases) which is incurable. Survival after 5 years is approximately 14% for patients with metastatic disease. Clinical trials using immunotherapy drugs called 'immune checkpoint inhibitors' have shown excellent results in advanced colorectal cancer patients who have certain genetic characteristics called 'mismatch repair deficiency (MMR-d)' and 'high microsatellite instability (MSI-h)'. The benefits of immunotherapy as a treatment prior to surgery to remove the tumour (neoadjuvant treatment) has been observed in both melanoma and in glioblastoma with enhanced local and systemic anti-tumour responses. Pembrolizumab is an immunotherapy drug and works by helping the body's own immune system to fight the cancer cells. The NEOPRISM-CRC trial will investigate whether giving pembrolizumab before surgery is safe, whether it improves the chances of the tumour being removed completely and whether it delays or prevents the cancer from coming back. Pembrolizumab treatment lasts for a maximum of 9 weeks (maximum of 3 cycles of treatment, each cycle consisting of 3 weeks) and is given prior to surgery. Following surgery patients will be followed up for at least 3 years after their surgery and to a maximum of 5 years. Target recruitment is 88 patients and recruitment is expected to take place over a 48 month period. Blood, tissue, mouth swabs and stool samples will be collected from patients throughout the trial to better understand the biology of immunotherapy as a treatment for CRC prior to surgery.

Key Dates

First listed
Jan 19, 2022
Start date
Jul 20, 2022
Status verified
Apr 2026
Primary completion
Jul 31, 2026
Completion
Jul 31, 2029

Study Design

Enrollment
88 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Tumour Mutation Burden high or medium (or MSI-High)
    Patients will one cycle of pembrolizumab 200 mg IV (a cycle is 21 days). Prior to cycle 2 the result of the FOUNDATIONONE®CDx test or FOUNDATIONONE® Liquid CDx should be available and patients will continue their treatment as follows: TMB-high (defined as ≥20 mutations per Mb) or medium (defined as 6-19 mutations per Mb); FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test (or MSI-H if FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test is not evaluable): * A further two cycles of pembrolizumab 200 mg IV every 21 days * Planned surgery to remove the CRC 4 - 6 weeks after last dose of pembrolizumab
  • Other: Tumour Mutation Burden low or unevaluable
    Patients will one cycle of pembrolizumab 200 mg IV (a cycle is 21 days). Prior to cycle 2 the result of the FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test should be available and patients will continue their treatment as follows: TMB-low (defined as ≤5 mutations per Mb); FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx OR if FOUNDATIONONE test and MSI result by PCR are both not evaluable): • Planned surgery to remove the CRC 4 - 6 weeks after last dose of pembrolizumab

Primary Outcome Measure

Relapse-free survival [ Time Frame: From registration to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date ]

Central Contacts

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