Vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer: a phase II study (COREVAX-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Apr 2016 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516221-31-00

EudraCT number

2015-000894-11

ClinicalTrials.gov

NCT02919644

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Safety and immunological efficacy of the treatment

Secondary objectives 7

1. Clinical outcome
2. To evaluate the predictive role of the development of a positive DTH test after at least three vaccine administrations
3. To evaluate the persistence of an antitumor immune response after the completion of the vaccination program.
4. To evaluate the prognostic or predictive role of the enhancement of a specific immune response.
5. To evaluate a panel of inflammatory cytokines involved in antitumor immune response.
6. To evaluate the predictive role of immune cells in tumour microenvironment.
7. To evaluate the predictive role of tumour antigen expression.

Conditions and MedDRA coding

Stage IV colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 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
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
10. The patient is willing and able to give written informed consent for the study

Exclusion criteria 13

1. Patients with residual disease after surgery. Marginal resection of any lesion in the absence of clinically evident residual disease is acceptable.
2. Patient who completed surgery more than 60 days before study enrolment
3. 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
4. History of congenital or acquired immunodeficiency, including history of organ transplantation.
5. Any positivity for the serologic markers of HBV (including at least anti-HBs antibodies and anti-HBc antibodies), HCV, HIV or Treponema pallidum
6. Female patients who are pregnant or nursing.
7. 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.
8. Participation in another clinical trial with any investigational agent within 30 days prior to study screening.
9. 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.
10. 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.
11. Any clinical condition that, in the opinion of the Investigator, contraindicates the subcutaneous administration of low-dose IL-2 as per protocol
12. 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.
13. Refusal of giving written informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Type, incidence, and severity of the adverse events
2. Quantification of the circulating immune effectors specific for a selected panel of tumour antigens
3. Immunohistochemistry on formalin-fixed, paraffin-embedded tumour samples will allow to evaluate the expression of tumour-associated antigen and to characterize the immune infiltrate.

Secondary endpoints 4

1. RFS, OS, TTP
2. The potential predictive role of immunological response, as assessed by ELISPOT and DTH skin test, will also be assessed.
3. Serum sampling will be performed before the first treatment cycle and at each disease restaging up to two years after treatment, to identify whether changes in markers values eventually found will predict disease relapse.
4. Serum sampling will also allow the evaluation of a panel of proinflammatory cytokines during and after treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Sponsor organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Francesco De Rosa

Public contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications