Clinical Trials /

A Phase II Trial Assessing Nivolumab in Strong Class II Expressing Microsatellite Stable Colorectal Cancer

NCT03981146

Description:

An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with strong class II expressing microsatellite stable colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Trial Assessing Nivolumab in Strong Class II Expressing Microsatellite Stable Colorectal Cancer
  • Official Title: A Phase II Trial Assessing Nivolumab in Strong Class II Expressing Microsatellite Stable Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: RG_17-215
  • SECONDARY ID: 2018-000318-39
  • SECONDARY ID: 40245896
  • NCT ID: NCT03981146

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
NivolumabNivolumab

Purpose

An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with strong class II expressing microsatellite stable colorectal cancer.

Detailed Description

      Immuno-oncology is transforming the care of certain patients with cancer. Not all patients
      respond to these therapies however, and in some common cancers checkpoint blockade has failed
      to make any real impact. In 2014 there were over 41,000 new cases of colorectal cancer (CRC)
      in the UK and nearly 16,000 deaths from the disease, making it the second commonest cause of
      cancer death (Cancer Research UK Cancer Statistics Key Facts). 15% of patients with CRC
      develop it as a result of deficient mismatch repair (microsatellite instability - MSI): this
      cohort of patients respond well to PD-1/PD-L1 blockade as these tumours harbour a very high
      number of mutations thus increasing the likelihood of the presence of immunogenic
      neo-epitopes which elicit an immune response1. The majority of CRC patients, particularly
      those with metastatic disease (around 95%), do not display this hyper-mutator phenotype
      (microsatellite stable (MSS) CRC) and in these patients the results of PD-1/PD-L1 blockade
      have been disappointing.

      In summary, MSS CRC patients with strong class II expression appears to represent
      immunologically a group of MSI-like MSS patients that may respond to usefully to the
      immunotherapy agent nivolumab as a single agent and thus a trial of nivolumab in patients
      with strong class II expression of their cancer cells appears to be highly justified.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalPatients will receive 240mg of Nivolumab on a two weekly cycle for a maximum of two years.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed locally advanced or metastatic MSS CRC with strong class II
             expression (greater than 50% cancer cell positivity for class II expression on
             immunohistochemistry).

               -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (APPENDIX 1)

               -  Age ≥ 18 years

               -  Patients must have completed all standard of care therapy that the treating
                  oncologist deems appropriate. Trial treatment as first line therapy is permitted
                  if the patient has declined standard of care therapy.

               -  CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating
                  unidimensionally measurable disease as per RECIST version 1.1 (APPENDIX 3).

               -  Demonstrate adequate haematological function:

                    -  Platelet count ≥100 x 109 /L

                    -  Neutrophils ≥1.5 x 109/L

                    -  Haemoglobin ≥ 90 g/L

               -  Demonstrate adequate hepatic function:

                    -  Serum bilirubin ≤1.5 x upper limit of normal (ULN)

                    -  Serum AST or ALT ≤2.5 x ULN or <5 x ULN in the presence of liver metastases

               -  Demonstrate adequate renal function

                  o Creatinine clearance <1.5 times ULN and >30ml/min (as per institutional
                  standard).

               -  Provision of signed and dated, written informed consent prior to any trial
                  specific procedures, sampling and analyses.

               -  Negative pregnancy test (female patients of reproductive potential). (Serum Test
                  must be negative)

               -  Patients must agree to the use of contraception as detailed in section 7.8

        Exclusion Criteria:

          -  Previous treatment with PD1/PDL1 inhibitors.

               -  Untreated symptomatic brain or leptomeningeal metastatic disease.

               -  Medical or psychiatric conditions compromising informed consent.

               -  Any medical condition which, in the opinion of the Investigator, would compromise
                  the ability of the patient to participate in the trial or which would jeopardise
                  compliance with the protocol.

               -  Administration of chemotherapy, radioactive or biological cancer therapy within 4
                  weeks prior to the first dose of trial therapy Patient has not recovered to CTCAE
                  grade 1 or better from the Adverse Event (AE) due to cancer therapeutics
                  administered more than 4 weeks earlier.

               -  Active autoimmune disease that has required systemic treatment in past 2 years
                  (i.e.

        with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

        Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement
        therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
        treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment. Patient has risk factors for bowel obstruction or bowel
             perforation (examples include but not limited to a history of acute diverticulitis,
             intra-abdominal abscess and abdominal carcinomatosis).

          -  Patient has a known history of other malignancy, unless the patient has undergone
             potentially curative therapy with no evidence of that disease for 3 years.

          -  Has a history of non-infectious pneumonitis requiring steroids or has active
             pneumonitis.

          -  Female patients that are either pregnant or breast feeding.

          -  Male and female patients (of childbearing age) not willing to use adequate
             contraception.

          -  Patient previously had a severe hypersensitivity reaction to treatment with another
             monoclonal antibody.

          -  Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies),
             active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is
             detected); patients with negative Hepatitis C antibody testing may not need RNA
             testing.

          -  Known history of tuberculosis.

          -  Patient has an active infection requiring therapy.

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment.

          -  Patient is, at the time of signing informed consent, a regular user (including
             "recreational use") of any illicit drugs or had a recent history (within the last
             year) of substance abuse (including alcohol).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Durable Clinical Benefit
Time Frame:Beginning of trial treatment to free of disease progression (104 weeks maximum)
Safety Issue:
Description:patient will be defined as experiencing DCB if they remain free of disease progression at their third trial specific CT scan since treatment start date (i.e. at approximately 27 weeks) or at any CT scan after 27 weeks that shows the patient remains free of disease progression

Secondary Outcome Measures

Measure:Objective response
Time Frame:trial treatment until disease progression (104 weeks maximum)
Safety Issue:
Description:Objective response is the occurrence of CR or PR as the best overall response
Measure:Best Percentage Change in Sum of Target Lesions
Time Frame:Trial Treatment to disease progression (104 weeks maximum)
Safety Issue:
Description:At each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment.
Measure:Time to Maximal Response
Time Frame:Occurrence of CR or PR during the trial (104 weeks maximum)
Safety Issue:
Description:This is defined as the time from commencement of trial treatment to the date of CT scan that first records the best objective response as per RECIST version 1.1.
Measure:Progression Free Survival Time
Time Frame:time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)
Safety Issue:
Description:This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression.first records the best objective response as per RECIST version 1.1.
Measure:Overall Survival Time
Time Frame:Trial Treatment to date of death.
Safety Issue:
Description:This is defined as the time from commencement of trial treatment to the date of death.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Birmingham

Trial Keywords

  • Strong Class II Microsatellite Status

Last Updated