Preoperative chemoradiotherapy with immunotherapy in rectal cancer

Phase 1

• Conditions: • 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; MedDRA version: 20.0Level: PTClassification code 10038038Term: Rectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10038045Term: Rectal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003865-17-AT
• Lead Sponsor: Medizinische Universität Wien

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-21
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Safety, tolerability and feasibility of standard neoadjuvant CRT with sequential ipilimumab and nivolumab following surgical resection. ;Secondary Objective: • Radiographic response determined by magnetic resonance imaging-assessed tumor regression grade (mrTRG)<br>• Pathological response determined by tumor regression grade (TRG) and tumor stage (ypT and ypN stage).;Primary end point(s): See primary objective;Timepoint(s) of evaluation of this end point: After surgery.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): See secondary objectives.;Timepoint(s) of evaluation of this end point: After surgery.