Neoadjuvant Chemoradiotherapy With Sequential Ipilimumab and Nivolumab in Rectal Cancer
Phase 2
Completed
- Conditions
- Rectal Cancer
- Interventions
- Registration Number
- NCT04124601
- Lead Sponsor
- Johannes Laengle, MD, PhD
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- 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
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
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Neoadjuvant Chemoradiotherapy Chemoradiotherapy Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days) Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab Chemoradiotherapy Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days) with sequential Ipilimumab (1 mg/kg IV on day 7) and Nivolumab (3 mg/kg IV on day 14, 28 and 42) Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab Ipilimumab Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days) with sequential Ipilimumab (1 mg/kg IV on day 7) and Nivolumab (3 mg/kg IV on day 14, 28 and 42) Neoadjuvant Chemoradiotherapy, Ipilimumab, Nivolumab Nivolumab Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days) with sequential Ipilimumab (1 mg/kg IV on day 7) and Nivolumab (3 mg/kg IV on day 14, 28 and 42)
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (safety and tolerability) 20 weeks Incidence of treatment-emergent adverse events will be assessed according to the latest "Clavien- Dindo Classification of surgical complications" and Common Terminology Criteria of Adverse Events (CTCAE).
- Secondary Outcome Measures
Name Time Method Radiographic therapy response between pre-and post-neoadjuvant treatment 20 weeks Radiographic therapy response will be determined by magnetic resonance imaging-assessed tumor regression grade (mrTRG)
Pathologic therapy response to neoadjuvant treatment 20 weeks Pathological therapy response will be determined according to the latest American Joint Committee on Cancer/International Union Against Cancer-Tumor Node Metastasis (AJCC/UICC-TNM) staging and tumor regression grade (TRG).
Trial Locations
- Locations (5)
State Hospital Wiener Neustadt
🇦🇹Wiener Neustadt, Lower Austria, Austria
Hospital North - Clinic Floridsdorf
🇦🇹Vienna, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
Congregational Hospital Linz - Sisters of Mercy
🇦🇹Linz, Austria
Hospital of St. John of God
🇦🇹Vienna, Austria