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

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ClinicalTrials.gov Identifier: NCT04124601
Recruitment Status : Not yet recruiting
First Posted : October 11, 2019
Last Update Posted : October 15, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Johannes Laengle, MD, PhD, Medical University of Vienna

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
Rectal Cancer Radiation: Chemoradiotherapy Drug: Ipilimumab Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Yervoy®

Drug: Nivolumab
Infusion
Other Name: Opdivo®




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (safety and tolerability) [ Time Frame: 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 [ Time Frame: 20 weeks ]
    Radiographic therapyresponse between pre-and post-neoadjuvant treatment will be determined by the response evaluation criteria in solid tumors 1.1 (RECIST 1.1), immune-related response criteria (irRC), immune (i)RECIST and/or immune-modified (im)RECIST.

  2. Pathologic therapy response to neoadjuvant treatment [ Time Frame: 20 weeks ]
    Pathological therapy response will be determined according to the latest the American Joint Committee on Cancer/International Union Against Cancer-Tumor Node Metastasis (AJCC/UICC-TNM) staging and tumor regression grade (TRG).



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin and/or curatively-resected in situ cervical and/or breast cancers
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124601


Contacts
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Contact: Johannes Laengle, MD, PhD +43 1 40400 69260 johannes.laengle@meduniwien.ac.at
Contact: Michael Bergmann, MD +43 1 40400 69260 michael.bergmann@meduniwien.ac.at

Locations
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Austria
State Hospital Wiener Neustadt Not yet recruiting
Wiener Neustadt, Lower Austria, Austria
Contact: Friedrich Laengle, MD    +43 2622 9004 22201    friedrich.laengle@wienerneustadt.lknoe.at   
Principal Investigator: Friedrich Laengle, MD         
Medical University of Vienna Not yet recruiting
Vienna, Austria, 1090
Contact: Johannes Laengle, MD, PhD    +43 1 40400 69260    johannes.laengle@meduniwien.ac.at   
Contact: Michael Bergmann, MD    +43 1 40400 69260    michael.bergmann@meduniwien.ac.at   
Sub-Investigator: Johannes Laengle, MD, PhD         
Principal Investigator: Michael Bergmann, MD         
Sponsors and Collaborators
Johannes Laengle, MD, PhD
Bristol-Myers Squibb
Investigators
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Principal Investigator: Michael Bergmann, MD Division of General Surgery, Department of Surgery, Medical University of Vienna

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Responsible Party: Johannes Laengle, MD, PhD, Sponsor-Investigator, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT04124601     History of Changes
Other Study ID Numbers: CA209-7HJ
2019-003865-17 ( EudraCT Number )
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, Medical University of Vienna:
Ipilimumab
Nivolumab
Chemoradiotherapy
Rectal cancer
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Nivolumab
Ipilimumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological