Intratumoral Flu Vaccine and Pembrolizumab in Colorectal Cancer

Phase 1

• Conditions: Colorectal Cancer; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-503228-17-00
• Lead Sponsor: Zealand University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-01
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Have histologically confirmed localized pMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colorectal carcinoma., Participants must use (or have their partner use) an acceptable method of contraception, during heterosexual activity, while receiving pembrolizumab and for 120 days after the administration., Women of reproductive potential (WORP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to receiving pembrolizumab., Women must not be breastfeeding., Have indication for elective curative intended surgery without neoadjuvant chemotherapy., Be = 18 years of age on the date of signing the informed consent., Provide written informed consent, Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1., Have adequate bone marrow function: Hemoglobin = 6.2 mmol/L or = 10 g/dL Absolute neutrophil count (ANC) = 1.5 × 109/L Platelet count = 100 × 109/L, Have adequate kidney function defined as Glomerular filtration rate (GFR) = 60 mL/min or creatinine =1.5 X upper limit of normal (ULN), Have adequate liver function defined as: Total bilirubin = 1.5 × ULN Alanine aminotransferase (ALT): = 2.5 × ULN Alkaline phosphatase: = 2.5 × ULN, Follow the conditions regarding fertility, pregnancy, and lactation: Female and male participants of reproductive potential (for definition refer to appendix 18) must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving pembrolizumab and for 120 days after the administration.

Exclusion Criteria

Has any serious or uncontrolled medical disorder that, in the opinion of the investigator or treating physician, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results., Acute febrile illness, Acute infectious disease, Highly inflamed gastrointestinal tissue which is ulcerated and bleeding, Has an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus)., Has received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody/drug specifically targeting T cell co-stimulation or checkpoint pathways., Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected)., Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease., Has received live vaccines within 30 days prior to first dose trial treatment (Examples of live vaccines include, but are not limited to: measles, mumps, rubella, chickenpox), Has recently received yellow fever, rabies, BCG, and typhoid (oral) vaccine., Has a history of allergy to study drug components or a history of severe hypersensitivity reaction to any monoclonal antibody, Any previous allergic reaction to influenza vaccine or constituents, egg and chicken proteins, neomycin, formaldehyde or octoxinol-9

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: This study aims to investigate whether a combination of local flu vaccine treatment and immunotherapy will cause tumor regression in patients with pMMR type colorectal cancer.;Secondary Objective: We will investigate specific safety events during the trial and will characterize the cancer-killing immune cells with different methods as well as characterize the functional changes in the tumor microenvironment;Primary end point(s): The primary endpoint will be that 50% or more patients achieve a major pathological response (MPR) that will be defined as < 10 % viable cells corresponding to Mandard tumor regression grade 1-2 (MTRG).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Specific safety outcomes including tumor site perforation and delay of surgery, and changes in the recovery as assessed by the QoR-15 questionnaire;Secondary end point(s):Analysis of tumor samples: Immunohistochemical analysis of CD3+ and CD8+ T cells, spatial protein expression analyses of immune-infiltrated regions of tumors at the different time points, flow cytometry, and full transcriptomic analyses including single cell analysis.;Secondary end point(s):Analysis of blood samples: flow cytometry and full transcriptomic analyses including single cell analysis.