Colorectal CancerPhase 2FLU-IMMUNENCT05909423
Combining Intratumoral Flu Vaccine and Systemic Pembrolizumab in Patients With Early pMMR Colorectal Cancer
A Phase 2 study testing Influenza vaccine and Pembrolizumab in people with Colorectal Cancer, run by Zealand University Hospital at 1 site in Denmark.
Trial summary
Immune checkpoint inhibitor (ICI) treatment has produced striking results in patients with colorectal cancer (CRC) of the subtype deficient mismatch repair (dMMR). The majority of patients, however, have proficient MMR (pMMR) tumors, with limited effect of ICIs. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Influenza vaccine and Pembrolizumab
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2023to 1 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have histologically confirmed localized pMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colorectal adenocarcinoma.
- Have indication for elective curative intended surgery without neoadjuvant therapy.
- 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:
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- 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:
- o 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 180 days after the administration.
- Participants must use (or have their partner use) an acceptable method of contraception, as outlined in the appendix 16, 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.
Who cannot join
- 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.
- 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,
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- 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
- Acute febrile illness
- Acute infectious disease
- Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Center for Surgical Science, Department of Surgery, Zealand University Hospital
Koege, Region Sjælland, 4600
About this study
Official title: Combining Intratumoral Flu Vaccine and Systemic Pembrolizumab in Patients With Early pMMR Colorectal Cancer - the FLU-IMMUNE Trial.
Immune checkpoint inhibitor (ICI) treatment has produced striking results in patients with colorectal cancer (CRC) of the subtype deficient mismatch repair (dMMR). The majority of patients, however, have proficient MMR (pMMR) tumors, with limited effect of ICIs. The key difference between dMMR and pMMR tumors is the infiltration of cytotoxic T-cells. dMMR tumors have increased infiltration and thus increased efficacy from ICI treatment. The investigators conducted a proof of concept study where the investigators applied an intratumoral (IT) unaltered flu vaccine in ten patients with non-metastatic pMMR CRC. The intervention increased infiltration of cytotoxic T-cells and the immune checkpoint PD-L1, suggesting that IT flu vaccine primes pMMR tumors to ICI treatment. The investigators aim to test the combination of IT flu vaccine and ICI treatment in patients with non-metastatic pMMR CRC in a new trial. The hypothesis is that IT flu vaccine and ICI treatment will synergistically to induce cancer cell death.
- Conditions
- Colorectal Cancer
- Being tested
- Influenza vaccine, Pembrolizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Influenza vaccineDrug
Intratumoral influenza vaccine treatment, administered via endoscopic procedure
PembrolizumabDrug
Single dose pembrolizumab treatment
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Intratumoral flu vaccine treatment Systemic single dose pembrolizumab treatment Receives: Drug: Influenza vaccine; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological response
The primary endpoint will be the percent of viable tumor cells in the resected specimen. Partial response will be defined as at least 30% tumor regression and major pathological response (MPR) will be defined as < 10 % viable cells corresponding to Mandard tumor regression grade 1-2
Measured: Day 30-35
Secondary outcomes (3)
Number of participants with specific treatment-related adverse events as assessed by CTCAE v4.0"
Intratumoral flu vaccine treatment:
The specific safety endpoint is perforation at tumor site due to intratumoral flu vaccine treatment
Pembrolizumab treatment:
Postponement of surgery, and surgical complication that leads to reoperation
The Departments of Surgery are responsible for assessment of the "Before pembrolizumab treatment" safety endpoint, while Department of Surgery and Oncology are responsible for assessment of the remaining safety endpoints. Causality assessment will be done by investigators or delegates with relevant experience by use of the WHO-UMC causality assessment system.
Measured: Day 0-365
Tumor microenvironment
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.
Measured: Day 0-35
Analysis of perturbations in the immune activity with a focus on effector and memory CD8+ T cells
Flow cytometry and full transcriptomic analyses including single cell analysis of effector and memory CD8+ T cells
Measured: Day 0-35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start1 Sep 2023 (estimated)
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Slagelse Hospital
- Responsible party
- Principal investigator, Ismail Gögenur, Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05909423
- Sponsor's protocol ID
- 2023-503228-17-00
- Other IDs
- 2023
- Acronym
- FLU-IMMUNE
- Status last verified
- Jun 2023
- First submitted
- 18 May 2023
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Intratumoral Flu Vaccine and Systemic Pembrolizumab in Patients With Early pMMR Colorectal Cancer - the FLU-IMMUNE Trial.
- ClinicalTrials.gov ID
- NCT05909423
- Acronym / sponsor ID
- FLU-IMMUNE / 2023-503228-17-00
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Collaborators
- Slagelse Hospital
- Study start
- 1 Sep 2023 (estimated)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 18 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Immune checkpoint inhibitor (ICI) treatment has produced striking results in patients with colorectal cancer (CRC) of the subtype deficient mismatch repair (dMMR). The majority of patients, however, have proficient MMR (pMMR) tumors, with limited effect of ICIs. The key difference between dMMR and pMMR tumors is the infiltration of cytotoxic T-cells. dMMR tumors have increased infiltration and thus increased efficacy from ICI treatment. The investigators conducted a proof of concept study where the investigators applied an intratumoral (IT) unaltered flu vaccine in ten patients with non-metastatic pMMR CRC. The intervention increased infiltration of cytotoxic T-cells and the immune checkpoint PD-L1, suggesting that IT flu vaccine primes pMMR tumors to ICI treatment. The investigators aim to test the combination of IT flu vaccine and ICI treatment in patients with non-metastatic pMMR CRC in a new trial. The hypothesis is that IT flu vaccine and ICI treatment will synergistically to induce cancer cell death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Influenza vaccine, Drug: PembrolizumabIntratumoral flu vaccine treatment Systemic single dose pembrolizumab treatment |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Have histologically confirmed localized pMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colorectal adenocarcinoma.
- Have indication for elective curative intended surgery without neoadjuvant therapy.
- 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.
Key exclusion criteria (12 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Influenza vaccineIntratumoral influenza vaccine treatment, administered via endoscopic procedure | Drug | Treatment arm |
| PembrolizumabSingle dose pembrolizumab treatment | Drug | Treatment arm |
Primary outcome
Pathological response
Time frame: Day 30-35
The primary endpoint will be the percent of viable tumor cells in the resected specimen. Partial response will be defined as at least 30% tumor regression and major pathological response (MPR) will be defined as < 10 % viable cells corresponding to Mandard tumor regression grade 1-2
3 secondary outcomes
Number of participants with specific treatment-related adverse events as assessed by CTCAE v4.0"
Time frame: Day 0-365
Tumor microenvironment
Time frame: Day 0-35
Analysis of perturbations in the immune activity with a focus on effector and memory CD8+ T cells
Time frame: Day 0-35
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Influenza vaccine and Pembrolizumab in people with Colorectal Cancer, run by Zealand University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ismail Gögenur, Professor, DMSc (26336426 ext. 0045, igo@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological response (time frame: Day 30-35). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.