Overview

This trial is active, not recruiting.

Conditions stage iv colorectal cancer, curative resection
Treatments autologous dendritic cells loaded with autologous tumour homogenate, il2
Phase phase 2
Target IL-2
Sponsor Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Start date April 2016
End date April 2019
Trial size 19 participants
Trial identifier NCT02919644, 2015-000894-11, IRST153.04

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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)
autologous dendritic cells loaded with autologous tumour homogenate
Each vaccine dose consists of 10_7 autologous dendritic cells loaded with autologous tumor homogenate
il2
Each vaccine dose is followed, after two days, by IL-2 as adjuvant, at a dose of 3 MU daily for five consecutive days

Primary Outcomes

Measure
safety
time frame: up to 24 months
immunological efficacy
time frame: up to 24 months

Secondary Outcomes

Measure
Relaps Free Survival (RFS)
time frame: up to 7 years
Overall Survival (OS)
time frame: up to 7 years
Positive Delayed Type Hypersensitivity (DTH) skin test
time frame: up 24 months
Antitumor Immune response
time frame: up to 7 years
evaluation of the prognostic or predictive role of the enhancement of a specific immune response
time frame: up to 7 years
evaluation of a panal of inflammatory cytokines involved in antitumor immune response
time frame: up to 24 months
evaluation of the predictive role of tumour antigen expression
time frame: up to 24 months
evaluation of the predictive role of immune cells in tumor microenvironment
time frame: up to 24 months

Eligibility Criteria

Male or female participants at least 19 years old.

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 IRST IRCCS and must fulfil all the acceptance criteria prescribed by the 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. 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. AST and 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 HBV (including at least anti-HBs antibodies and anti-HBc antibodies), 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 leukoaphaeresis). 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 leukaphaeresis. 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.

Additional Information

Official title Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer: a Phase II Study
Principal investigator Francesco De Rosa, MD
Description 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 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 minmax 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori.