Neoadjuvant Chemoradiotherapy With Sequential Ipilimumab and Nivolumab in Rectal Cancer (CHINOREC)

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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Chemoradiotherapy; Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4010
    • Congregational Hospital Linz - Sisters of Mercy
  • Vienna, Austria, 1090
    • Medical University of Vienna
  • Vienna, Austria, 1020
    • Hospital of St. John of God
  • Vienna, Austria, 1210
    • Hospital North - Clinic Floridsdorf
  • Lower Austria
    • Wiener Neustadt, Lower Austria, Austria
      • State Hospital Wiener Neustadt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Neoadjuvant Chemoradiotherapy; Neoadjuvant Chemoradiotherapy (50 Gy in 2 Gy fractions + Capecitabine 1650 mg/m2/d over 25 working days)	Radiation: Chemoradiotherapy; Capecitabine tablet with fractionated radiotherapy; Other Names: Chemoradiation; Radiochemotherapy
Experimental: Neoadjuvant Chemoradiotherapy, Ipilimumab, 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)	Radiation: Chemoradiotherapy; Capecitabine tablet with fractionated radiotherapy; Other Names: Chemoradiation; Radiochemotherapy; Drug: Ipilimumab; Infusion; Other Names: Yervoy®; Drug: Nivolumab; Infusion; Other Names: Opdivo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Johannes Laengle, MD, PhD
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Michael Bergmann, MD, Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 20, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Rectal cancer; Ipilimumab; Chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-7HJ; 2019-003865-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes