Immunotherapy in Patients With Early dMMR Rectal Cancer
ConditionCancer of Rectum
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorOdense University Hospital
About this trial
The purpose of this investigator-initiated, multicenter phase II trial is to evaluate the efficacy and tolerability of nivolumab and ipilimumab in patients with stage 1-3 MSI/dMMR rectal cancer.
The primary objective is:
Number of patients with complete clinical response after one or two cycles of immunotherapy.
Patients will be treated with 1 or 2 cycles of combination immunotherapy:
Cycle 1: Nivolumab 3 mg/kg days 1 and 15 \& ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 \& ipilimumab 1 mg/kg day 50
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years.
Histologically verified non-metastatic rectal cancer stage 1-3.
No indication for local therapy like TEM.
Histologically verified dMMR or MSI.
Disqualifiers
Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
Concomitant use of systemic glucocorticoids more than the equivalent dose to tablet prednisolone 10 mg/day. Treatment with systemic glucocorticoids must end no later than two weeks before inclusion.
Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
Known allergy or intolerance to any of the drugs used (nivolumab and ipilimumab).
Trial design
Design model
Single group
Treatments tested in this trial
Nivolumab
DrugNivolumab is a highly selective fully humanized, IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1) (17). PD-1 is an inhibitory receptor expressed on the surface of T-cells, B cells, macrophages, and NK cells. Endogenous binding of PD-1 with one of its two ligands PD-L1 and PD-L2 results in production of an inhibitory signal which results in reduction of T-cell proliferation, cytokine production, and cytotoxic activity. This results in significant dampening of the immune response. Nivolumab acts to selectively block the receptor activation of PD-L1 and PD-L2, resulting in a release of PD-1 mediated inhibition of the immune response.
Ipilimumab
DrugIpilimumab is a fully humanized monoclonal anti-CTLA-4 antibody that acts as an antineoplastic ICI by selectively binding to cytotoxic T-lymphocyte-associated antigen 4, a molecule located on the surface of cytotoxic T-cells, suppressing the immune response (17). Ipilimumab blocks CTLA-4, leading to a continuously active immune response in malignant cells.
Treatment groups
39 Participants
are divided into 1 treatment groupGroup A: nivolumab + ipilimumabExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Complete clinical response
Proportion of patients with complete clinical response Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.
Time frame
Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)Secondary outcomes
1
Complete biological response
Proportion of patients with complete biological response
Time frame
Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)2
12 months recurrence
Proportion of patients without any sign of recurrence after 12 months.
Time frame
after 12 months3
Respons rate
Response rate according to mrTRG.
Time frame
after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)4
Adverse events
Adverse events assessed by the investigator according to the definitions in NCI-CTC, version 5.0
Time frame
after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Odense University Hospital
Lead sponsor
Rigshospitalet, Denmark
Collaborator
Zealand University Hospital
Collaborator
Aalborg University Hospital
Collaborator
Aarhus University Hospital
Collaborator
Bispebjerg Hospital
Collaborator
Herlev and Gentofte Hospital
Collaborator
Vejle Hospital
Collaborator
Source ClinicalTrials.gov