A phase II study on adjuvant vaccination with dendritic cells loaded with autologous tumor homogenate in resected stage IV rare cancers: neuroendocrine tumors (NET) and soft tissue sarcoma (STS).

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

12 Dec 2019 → ongoing

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-510251-31-00

EudraCT number

2019-000793-27

ClinicalTrials.gov

NCT04166006

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

Safety and immunological efficacy

Secondary objectives 7

1. Clinical outcome
2. Predictive role of a positive DTH test after 3 vaccine administrations
3. Prognostic/predictive role of specific cell-mediated immune response
4. Persistence of antitumor immune response
5. Serum level of proinflammatory/ pro-angiogenic factors
6. Predictive role of immune cells in the peripheral blood and in the tumour microenvironment
7. Predictive role of tumour antigen expression in tumour tissue

Conditions and MedDRA coding

neuroendocrine tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patients must have histologically confirmed stage IV NeuroEndocrine Tumors (NET) or Soft Tissue Sarcoma (STS), surgically treated with radical intent.
2. The autologous surgical specimen must have been collected and sent to the Somatic Cell Therapy Lab of IRCCS IRST 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 occurred in other sites, these must be also included in the baseline CT scan and in all the subsequent evaluations.
4. Patients disease-free candidates for only observation as per clinical practice (no standard treatment is available after surgery)
5. The patient must have recovered (grade 1 or less by CTCAE 5.0) from all the adverse events related to previous surgery.
6. Age ≥18 years
7. ECOG performance status 0 or 1
8. Patient must have acceptable organ function, defined as: a. Haemoglobin >10 g/dl b. White blood cells ≥3000/μl. c. Absolute neutrophil count ≥1500/μl. d. Platelets≥75000/μl. e. AST and ALT <3 times the upper institutional reference level. f. Total bilirubin <1.5 times the upper institutional reference level. g. Serum creatinine <1.5 times the upper institutional reference level.
9. Patients aged 70 years or older must have left ventricular ejection fraction not lower than 55% as assessed by echocardiography
10. 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 the patients’ lifestyle guarantees his/her strict compliance with this prescription in the judgement of the Investigator.
11. The patient is willing and able to give written informed consent for the study

Exclusion criteria 11

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 90 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. Female patients who are pregnant or breastfeeding.
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. Participation in another clinical trial with any investigational agent within 30 days prior to study screening
8. 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
9. 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.
10. 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
11. Refusal of giving written informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of patients experiencing grade 3 or higher adverse events
2. Number of patients showing enhancement in the proportion of circulating immune effectors specific for a selected panel of associated antigens for each disease

Secondary endpoints 3

1. Overall survival; relapse-free survival
2. Proportion of patients with positive DHT test will be calculated and the predictive role will be analyzed taking account of the relationship with the primary and the other secondary outcomes
3. All the immunological objectives will be calculated in terms of proportion and the correlation with efficacy and safety parameters will be explored

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

Laura Ridolfi

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

Application history

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