Vaccination using patients' own dendritic cells after surgery for advanced colorectal cancer

Vaccination with Autologous Dendritic Cells Loaded with Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer: a Phase II Study

This study is testing a new vaccine made from patients' own immune cells to see if it helps people with advanced colorectal cancer stay cancer-free after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Meldola, FC and 1 other locations)
• Trial ID: NCT02919644 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and immunological efficacy of a vaccination approach using autologous dendritic cells loaded with the patient's own tumor homogenate following curative resection of stage IV colorectal cancer. The study is designed as a single-arm, monocentric trial, where patients will receive the vaccine and their immune responses will be monitored. The primary objective is to assess the enhancement of circulating immune effectors specific to colorectal cancer antigens, while secondary objectives include evaluating clinical outcomes and the persistence of the immune response. The trial follows a two-stage design to determine if further studies are warranted based on immune response rates.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years with histologically confirmed stage IV colorectal cancer who have undergone curative surgical resection and are disease-free.

Not a fit: Patients with active disease or those who have not recovered from previous surgeries may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the immune response against colorectal cancer, potentially improving patient outcomes and survival rates.

How similar studies have performed: While similar immunotherapy approaches have shown promise in other cancers, this specific method using autologous dendritic cells in stage IV colorectal cancer is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Patients must have histologically confirmed stage IV colorectal cancer surgically treated with radical intent.
2. The autologous surgical specimen must have been collected and sent to the Somatic Cell Therapy Lab of Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS) and must fulfil all the acceptance criteria prescribed by the Good Manufacturing practise (GMP) procedures.
3. The patient must be disease-free, as assessed by CT scan or MRI of the chest, abdomen, pelvis performed within 60 days before enrolment. If the resected lesions had occurred in other sites, these must be also included in the baseline CT scan and in all the subsequent evaluations.
4. The patient must have recovered (grade 1 or less by CTCAE 4.0) from all the adverse events related to previous surgery.
5. Age \>18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Patient must have acceptable organ function, defined as:

   1. Haemoglobin \>10 g/dl
   2. White blood cells ≥4000/μl.
   3. Absolute neutrophil count \>1500/μl.
   4. Platelets ≥100000/μl.
   5. aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) \<3 times the upper institutional reference level.
   6. Total bilirubin \<1.5 times the upper institutional reference level.
   7. Serum creatinine \<1.5 times the upper institutional reference level.
8. Patients aged 70 years or older must have left ventricular ejection fraction not lower than 55% as assessed by echocardiography.
9. Female patients of childbearing potential and all male patients must accept and be compliant with an highly effective contraceptive method (i.e. with a failure rate of \<1% per year: double barrier method, one barrier method plus spermicidal, intrauterine device, or oral contraception) from informed consent signature and up to three months after end of study. For this purpose are considered of childbearing potential all female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile. Complete abstinence from sexual intercourses is acceptable if patients' lifestyle guarantees his/her strict compliance with this prescription in the judgement of the Investigator.
10. The patient is willing and able to give written informed consent for the study.

Exclusion Criteria:

1. Patients with residual disease after surgery. Marginal resection of any lesion in the absence of clinically evident residual disease is acceptable.
2. Patients who relapsed within 6 months since primary treatment of stage I-III colorectal cancer. If adjuvant chemotherapy had been administered, the term must be computed since last chemotherapy dose.
3. Patient who completed surgery more than 60 days before study enrolment.
4. History of other neoplastic diseases in the previous 5 years, except basal cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with curative surgery.
5. History of congenital or acquired immunodeficiency, including history of organ transplantation.
6. Any positivity for the serologic markers of hepatitis B virus (HBV) (including at least anti-HBs antibodies and anti-hepatitis B core (HBc) antibodies), hepatitis C virus (HCV), HIV or Treponema pallidum. The serologic tests must have been performed within 30 days before any GMP-regulated activity (i.e. surgical resection and leukapheresis). The sole positivity for antibodies against the HBV S antigen (i.e. with all other HBV markers negative) is indicative of previous HBV vaccination and therefore is acceptable.
7. Female patients who are pregnant or nursing.
8. Patients undergone surgery after preoperatory chemotherapy with a fluoropyrimidine plus oxaliplatin, unless they are not candidate for postoperatory chemotherapy with the same schedule in the opinion of the Investigator (e.g. for unacceptable toxicity) or refuse completion of the perioperatory treatment.
9. Participation in another clinical trial with any investigational agent within 30 days prior to study screening.
10. Any active inflammatory or autoimmune disease requiring systemic steroids or other immunomodulatory agents as detailed in section 6.4, or potentially requiring such treatments during the study treatment in the judgement of the Investigator.
11. Any clinical condition that, in the opinion of the Investigator or the Transfusion Medicine specialist, is a contraindication to leukapheresis. In addition, all patients aged 70 or older must be evaluated by a cardiology specialist before the procedure to exclude any clinically relevant cardiac condition and any grade 3-4 cardiac arrhythmia, even if asymptomatic.
12. Any clinical condition that, in the opinion of the Investigator, contraindicates the subcutaneous administration of low-dose IL-2 as per protocol (see section 6.2 for details).
13. Any uncontrolled serious intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations potentially impacting patient safety and compliance in the opinion of the Investigator.
14. Refusal of giving written informed consent.

Where this trial is running

Meldola, FC and 1 other locations

• UO Immunoterapia e Laboratorio TCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l IRCCS — Meldola, Fc, Italy (Recruiting)
• CRO-IRCCS Aviano — Aviano, Italy (Not_yet_recruiting)

Study contacts

• Principal investigator: Francesco De Rosa, MD — UO Immunoterapia e Laboratorio TCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l IRCCS
• Study coordinator: Oriana Nanni, PhD

Conditions Stage IV Colorectal Cancer; Curative Resection; vaccination; autologous dendritic cells; autologous tumour homogenate; curative resection; stage IV colorectal cancer