Neoadjuvant Chemoradiotherapy With Sequential Ipilimumab and Nivolumab in Rectal Cancer

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.