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Vaccines

autologous dendritic cells loaded with autologous tumour homogenate given by intradermal injection (day 1), followed by IL-2 given by subcutaneous injection daily for five days (days 3-7)

Each vaccine dose consists of 10_7 autologous dendritic cells loaded with autologous tumor homogenate

autologous dendritic cells loaded with autologous tumour homogenate

Each vaccine dose is followed, after two days, by IL-2 as adjuvant, at a dose of 3 MU daily for five consecutive days

Oriana Nanni, PhD

Francesco De Rosa, MD

Angela Buonadonna, MD

Single-arm, monocentric trial to assess safety and immunological efficacy of adjuvant vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer

Vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer: a phase II study.

Primary objectives: Safety Immunological efficacy, expressed as number of patients who show enhancement of the proportion of circulating immune effectors specific for a selected panel of Colon-Rectal Cancer (CRC)-associated antigens.

Secondary objectives: Clinical outcome of the patients (OS, RFS, TTR). To evaluate the predictive role of the development of a positive DTH test after at least three vaccine administrations.

To evaluate the persistence of an antitumor immune response after the completion of the vaccination program.

To evaluate the prognostic or predictive role of the enhancement of a specific immune response.

To evaluate a panel of inflammatory cytokines involved in antitumor immune response.

To evaluate the predictive role of immune cells in tumour microenvironment. To evaluate the predictive role of tumour antigen expression.

This is a two-stage, phase 2 clinical trial designed according to Simon minimax design. A 40% immune response rate would preclude further studies, while a 70% immune response rate would indicate that further studies would be warranted. Given α and β error of 0.1, the first stage will require enrolment of 7 patients. If at least 3 patients show an immune response and toxicity is acceptable, the study will proceed to the second stage and additional 12 patients will be enrolled.

The vaccine will be considered immunologically active if at least 11 patients are immunological responders.

Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer.

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

To characterize the safety of the study drugs all adverse events observed during the study will be collected and assessed using the CTCAE v 4.03 criteria . Type, incidence, and severity of the adverse events will be reported and analyzed using descriptive statistics. All patients who received at least one treatment cycle will be considered evaluable for this primary endpoint.

Immunological efficacy will be assessed by quantifying circulating immune effectors specific for a selected panel of tumour antigens using interferon (IFN) - γELISPOT analysis . The assay determines the proportion of peptide-reactive T lymphocytes from peripheral blood mononuclear cells (PBMC) expressed as number of spot-forming Cells

Relapse Free Survival (RFS) is calculated as the time from study enrolment to either disease recurrence, defined as above, or the date of death for any cause. Patients alive with no evidence of disease recurrence at the time of their last visit are censored at the time of the last examination.

Overall Survival (OS) is calculated as the time from study enrolment to the date of death for any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.

evaluation of the predictive role of a positive DTH test after at least three vaccine administrations

evaluation of the persistence of an antitumor immune response after the completion of the vaccination program assessed by ELISPOT assays

evaluation of the prognostic or predictive role of the enhancement of a specific immune response assessed by ELISPOT

Serum sampling will allow the evaluation of a panel of inflammatory cytokines during and after treatment and their concentration will be evaluated by SearchLight multiplex array analysis according to manufacturer's instructions (FDA-validated test)

Immunohistochemistry on formalin-fixed, paraffin-embedded tumour samples will allow to evaluate the expression of tumour-associated antigen

Immunohistochemistry on formalin-fixed, paraffin-embedded tumour samples will allow to characterize the immune infiltrate

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer.	NCT02919644	Stage IV Colore... Curative Resect...	autologous dend... IL2	19 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer.	NCT02919644	Stage IV Colore... Curative Resect...	autologous dend... IL2	19 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Spots Global Cancer Trial Database for autologous tumour homogenate