NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer
ConditionAdenocarcinoma of the Colon
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity College, London
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically proven adenocarcinoma of the colon or rectum which is MMR-d by IHC or MSI-H by PCR (or microsatellite testing if routine practice).
Radiological node positive T1-4 CRC or
Node negative high risk T3 defined as EITHER ≥ 5mm of extramural depth of invasion OR unequivocal EMVI on imaging (regardless of depth) or Node negative T4 disease
Patients with rectal cancer are eligible if it is determined that neoadjuvant chemo-radiotherapy is not required to achieve a R0 resection.
Disqualifiers
Any patient for whom radiotherapy is advised by the MDT
Strong evidence of distant metastases or peritoneal nodules (M1)
Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration.
Trial design
Design model
Parallel
Treatments tested in this trial
Pembrolizumab
DrugDose: 200mg by IV infusion on Day 1 of each treatment cycle
Pembrolizumab
DrugDose: 200mg by IV infusion on Day 1 of Cycle 1 only
Treatment groups
88 Participants
are divided into 2 treatment groupsGroup A: Tumour Mutation Burden high or medium (or MSI-High)Other 1 intervention
Group B: Tumour Mutation Burden low or unevaluableOther 1 intervention
Trial outcomes
Primary outcomes
1
Relapse-free survival
Relapse-free Survival (RFS) is defined as time from start of treatment to time of any signs or symptoms of the cancer or time of death from any cause.
Time frame
From registration to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery dateSecondary outcomes
1
Pathological complete response rate (pCR)
A pCR will be defined as having no residual cancer cells in the resected specimen at surgery. Patients who do not achieve pCR or who do not proceed to resectional surgery for any reason will be counted as non-responders.
Time frame
Pathological complete response rate (pCR) assessed at 3 months following surgery2
Overall survival
Overall survival (OS) is defined as the time from start of treatment to time of death from any cause.
Time frame
From registration to death from any cause, assessed up to a maximum of 3 years from surgery date3
Frequency and severity of adverse events
Adverse events recorded continuously in relation to each treatment cycle graded using CTCAE criteria
Time frame
From informed consent to 3 months after surgery4
Rate of R0 resection and completed surgery
The incidence of resection types (R0, R1 and R2) will be presented in tables using frequencies, as well as the rate of surgery completed.
Time frame
Assessed from surgery to 28-35 days following surgerySponsors and contacts
Click on the lead sponsor to view all of their trials.
University College, London
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Sharp
Collaborator
Foundation Medicine
Collaborator
University College London (UCL) Cancer Institute
Collaborator
University of Leeds
Collaborator
University College London Hospitals
Collaborator
Personalis Inc.
Collaborator
Source ClinicalTrials.gov