Neoadjuvant Chemoradiotherapy With Sequential Ipilimumab and Nivolumab in Rectal Cancer

Rectal Cancer Clinical Trial

— CHINOREC  

Official title:

Neoadjuvant CHemoradiotherapy With Sequential Ipilimumab and NivOlumab in RECtal Cancer (CHINOREC): a Prospective Randomized, Open-label, Multicenter, Phase II Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04124601
• Other study ID #: CA209-7HJ
• Secondary ID: 2019-003865-17
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2020
• Est. completion date: March 15, 2024

Study information

• Verified date: April 2024
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 15, 2024
• Est. primary completion date: March 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Radiation:
• Chemoradiotherapy
Capecitabine tablet with fractionated radiotherapy

Drug:
• Ipilimumab
Infusion
• Nivolumab
Infusion

Locations

Country	Name	City	State
Austria	Congregational Hospital Linz - Sisters of Mercy	Linz
Austria	Hospital North - Clinic Floridsdorf	Vienna
Austria	Hospital of St. John of God	Vienna
Austria	Medical University of Vienna	Vienna
Austria	State Hospital Wiener Neustadt	Wiener Neustadt	Lower Austria

Sponsors (2)

Lead Sponsor	Collaborator
Johannes Laengle, MD, PhD	Bristol-Myers Squibb

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (safety and tolerability)	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).	20 weeks
Secondary	Radiographic therapy response between pre-and post-neoadjuvant treatment	Radiographic therapy response will be determined by magnetic resonance imaging-assessed tumor regression grade (mrTRG)	20 weeks
Secondary	Pathologic therapy response to neoadjuvant treatment	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).	20 weeks