Description:
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of
durable clinical benefit of nivolumab in patients with class II expressing microsatellite
stable colorectal cancer.
Title
- Brief Title: A Phase II Trial Assessing Nivolumab in Class II Expressing Microsatellite Stable Colorectal Cancer
- Official Title: A Phase II Trial Assessing Nivolumab in 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
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | | Nivolumab |
Purpose
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of
durable clinical benefit of nivolumab in patients with 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 a class II expression appear 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 class II
expression of their cancer cells appears to be highly justified.
Trial Arms
Name | Type | Description | Interventions |
---|
Nivolumab | Experimental | Patients will receive 480mg of Nivolumab on a four weekly cycle for a maximum of two years. | |
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed locally advanced or metastatic MSS CRC with class II
expression (greater than 1% 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
- Class II Microsatellite Status
Last Updated
November 6, 2020