A Phase II Study on Adjuvant Vaccination with Dendritic Cells Loaded with Autologous Tumor Homogenate in Resected Stage IV Rare Cancers.

This is a single-arm, multi-cohort phase II study, to evaluate the immunological effectiveness and safety of adjuvant Dendritic Cell (DC) vaccination. The evaluation of immunological efficacy will be expressed as the number of patients who show enhancement of the proportion of circulating immune effectors specific for a selected panel of associated antigens for each disease (HNSCC, NET and STS). To avoid unacceptable toxicity, a formal safety analysis will be conducted after six patients have been observed (two for each disease) for at least 30 days after the third treatment cycle. If two or more patients have experienced grade 3 or higher adverse events, enrollment will be definitively stopped; differently, other 15 patients for each disease will be enrolled and evaluation of primary objectives will be done for each cohort separately (H&N, STS and NET).

Inclusion criteria

• Patients must have histologically confirmed stage IV Head&Neck Squamous Cell Carcinoma (HNSCC), NeuroEndocrine Tumors (NET) or Soft Tissue Sarcoma (STS) surgically treated with radical intent.
• The autologous surgical specimen must have been collected and sent to the Somatic Cell Therapy Lab and must fulfil all the acceptance criteria prescribed by the Good Manufactory Practice (GMP) procedures.
• 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.
• Patients disease-free candidates for only observation as per clinical practice (no standard treatment is available after surgery)
• The patient must have recovered from all the adverse events related to previous surgery.
• Age ≥18 years.
• Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Patient must have acceptable organ function, defined as:

• Haemoglobin >10 g/dl
• White blood cells ≥3000/μl.
• Absolute neutrophil count ≥1500/μl.
• Platelets≥75000/μl.
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 times the upper institutional reference level.
• Total bilirubin <1.5 times the upper institutional reference level.
• Serum creatinine <1.5 times the upper institutional reference level.
• Patients aged 70 years or older must have left ventricular ejection fraction not lower than 55% as assessed by echocardiography.
• 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.
• The patient is willing and able to give written informed consent for the study.

Exclusion criteria

• Patients with residual disease after surgery. Marginal resection of any lesion in the absence of clinically evident residual disease is acceptable.
• Patient who completed surgery more than 90 days before study enrolment.
• 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.
• History of congenital or acquired immunodeficiency, including history of organ transplantation.
• Any positivity for the serologic markers of hepatitis B virus (HBV) (including at least anti- Hepatitis B surface antibodies (HBs) and 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 surface antigen (i.e.

with all other HBV markers negative) is indicative of previous HBV vaccination and therefore is acceptable.

• Female patients who are pregnant or nursing.
• Participation in another clinical trial with any investigational agent within 30 days prior to study screening.
• 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.
• 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.
• 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.
• Refusal of giving written informed consent.