neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer

Conditions: Rectal Cancer

Summary: this prospective randomized, open-label, multicenter, phase ii clinical trial investigates the safety and tolerability of standard neoadjuvant chemoradiotherapy (crt) with sequential ipilimumab and nivolumab in rectal cancer.


Eligibility criteria:
inclusion criteria: * 18 years of age and older * all sexes * histologically confirmed carcinoma of the rectum * suitable for local therapy with curative intent * medical need for a standard neoadjuvant crt * suitable to withstand a course of standard neoadjuvant crt * written informed consent form (icf) for participation in the study * eastern cooperative oncology group (ecog) performance status of 0 or 1 exclusion criteria: * metastatic disease that is considered incurable by local therapies * previous surgery of the tumor other than biopsy * pregnancy, breastfeeding or expectancy to conceive * disagreement of participants with reproductive potential to use contraception throughout the study period and for up to 180 days after the last dose of study therapy * prior therapy with anti-ctla-4, anti-pd-1, anti-pd-l1, anti-pd-l2 or any other agent directed against co-inhibitory t cell receptors or has previously participated in clinical studies with immunotherapy * any contraindication according to the official medical information of ipilimumab or nivolumab * live vaccine within 30 days prior to the first dose of study therapy * hepatitis b or c * human immunodeficiency virus (hiv) * immunodeficiency * allogeneic tissue or solid organ transplantation * autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, steroids or immunosuppressive drugs * systemic steroids or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment * active non-infectious pneumonitis * active infection requiring systemic therapy * treatment with botanical preparations (i.e. herbal supplements or traditional chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment * participants with serious or uncontrolled medical disorders * uncontrolled or significant cardiovascular disease (myocardial infarction, uncontrolled angina, any history of clinically significant arrhythmias, qtc prolongation in males \> 450 ms and \> 470 ms in females, participants with history of myocarditis) * allergies and adverse drug reaction (history of allergy or hypersensitivity to study drug components, contraindications to any of the study drugs of the chemotherapy regimen) * other exclusion criteria: prisoners or participants who are involuntarily incarcerated, participants who are compulsorily detained for treatment of either a psychiatric or physical (i.e. infectious disease) illness * white blood cells \< 2000/μl (si: \< 2.00 × 109/l) * neutrophils \< 1500/μl (si: \< 1.50 × 109/l) * platelets \< 100 × 103/μl (si: \< 100 × 109/l) (transfusions not permitted within 72 h prior to qualifying laboratory value) * hemoglobin \< 9.0 g/dl (si: \< 90 g/l) (transfusions not permitted within 72 h prior to qualifying laboratory value) * serum creatinine \> 1.5 × upper limit of normal (uln) or calculated creatinine clearance \< 50 ml/min (using the cockcroft-gault formula) * ast/alt: \> 3.0 × uln * total bilirubin \> 1.5 × uln (except participants with gilbert syndrome who must have a total bilirubin level of \< 3.0 × uln) * troponin t (tnt) or i (tni) \> 2 × institutional uln. tnt or tni levels between \> 1 to 2 × uln will be permitted to participate in the study if a repeat assessment remains 2 × uln and participant undergoes a cardiac evaluation. when repeat levels within 24 h are not available, a repeat test should be conducted as soon as possible.

Keywords: ipilimumab nivolumab chemoradiotherapy rectal cancer