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

Colorectal Cancer Clinical Trial

— ANICCA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03981146
• Other study ID #: RG_17-215
• Secondary ID: 2018-000318-3940
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 28, 2019
• Est. completion date: July 1, 2024

Study information

• Verified date: May 2024
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: July 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Nivolumab
60 Minute IV Infusion

Locations

Country	Name	City	State
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	St James Leeds	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Clatterbridge Cancer Centre	Liverpool
United Kingdom	Guys Hospital	London
United Kingdom	The Royal Free Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	University College Hospital	London
United Kingdom	The Christie Hospital, The Christie NHS Foundation Trust	Manchester
United Kingdom	Freemans Hospital	Newcastle Upon Tyne
United Kingdom	Weston Park	Sheffield

Sponsors (2)

Lead Sponsor	Collaborator
University of Birmingham	Bristol-Myers Squibb

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Durable Clinical Benefit	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	Beginning of trial treatment to free of disease progression (104 weeks maximum)
Secondary	Objective response	Objective response is the occurrence of CR or PR as the best overall response	trial treatment until disease progression (104 weeks maximum)
Secondary	Best Percentage Change in Sum of Target Lesions	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.	Trial Treatment to disease progression (104 weeks maximum)
Secondary	Time to Maximal Response	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.	Occurrence of CR or PR during the trial (104 weeks maximum)
Secondary	Progression Free Survival Time	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.	time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)
Secondary	Overall Survival Time	This is defined as the time from commencement of trial treatment to the date of death.	Trial Treatment to date of death.

External Links

•   Trial Website