E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
• 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 |
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E.1.1.1 | Medical condition in easily understood language |
• Rectal cancer • Medical need for a standard preoperative chemoradiotherapy • Suitable to withstand a course of standard preoperative chemoradiotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038038 |
E.1.2 | Term | Rectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038045 |
E.1.2 | Term | Rectal cancer NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety, tolerability and feasibility of standard neoadjuvant CRT with sequential ipilimumab and nivolumab following surgical resection. |
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E.2.2 | Secondary objectives of the trial |
• Radiographic response determined by magnetic resonance imaging-assessed tumor regression grade (mrTRG) • Pathological response determined by tumor regression grade (TRG) and tumor stage (ypT and ypN stage). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
See secondary objectives. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |