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CHINOREC: Neoadjuvant Chemoradiotherapy With Sequential Ipilimumab and Nivolumab in Rectal Cancer

Sponsor
Johannes Laengle, MD, PhD (Other)
Overall Status
Recruiting
CT.gov ID
NCT04124601
Collaborator
Bristol-Myers Squibb (Industry)
80
Enrollment
5
Locations
2
Arms
43
Anticipated Duration (Months)
16
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Neoadjuvant CHemoradiotherapy With Sequential Ipilimumab and NivOlumab in RECtal Cancer (CHINOREC): a Prospective Randomized, Open-label, Multicenter, Phase II Clinical Trial
Actual Study Start Date :
Jun 1, 2020
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

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:
  • Radiochemotherapy
  • Chemoradiation

    		•
    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:
  • Radiochemotherapy
  • Chemoradiation

    • Drug: Ipilimumab
    Infusion
    Other Names:
  • Yervoy®

    • Drug: Nivolumab
    Infusion
    Other Names:
  • Opdivo®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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)

    2. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 State Hospital Wiener Neustadt Wiener Neustadt Lower Austria Austria
    2 Congregational Hospital Linz - Sisters of Mercy Linz Austria 4010
    3 Hospital of St. John of God Vienna Austria 1020
    4 Medical University of Vienna Vienna Austria 1090
    5 Hospital North - Clinic Floridsdorf Vienna Austria 1210

    Sponsors and Collaborators

    • Johannes Laengle, MD, PhD
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Michael Bergmann, MD, Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Johannes Laengle, MD, PhD, Sponsor-Investigator, Medical University of Vienna
    ClinicalTrials.gov Identifier:
    NCT04124601
    Other Study ID Numbers:
    • CA209-7HJ
    • 2019-003865-17
    First Posted:
    Oct 11, 2019
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Johannes Laengle, MD, PhD, Sponsor-Investigator, Medical University of Vienna
    Ipilimumab
    Nivolumab
    Chemoradiotherapy
    Rectal cancer
    Additional relevant MeSH terms:
    Rectal Neoplasms
    Nivolumab
    Ipilimumab

    Study Results

    No Results Posted as of Mar 29, 2022