a phase ii, open-label trial evaluating gv1001 in advanced hepatocellular carcinoma.

Conditions: Carcinoma, Hepatocellular

Summary: the purpose of this study is to investigate the efficacy of gv1001 in locally advanced or metastatic hcc. also the safety of gv1001 and immunogenicity will be evaluated.


Eligibility criteria:
inclusion criteria: * hepatocellular carcinoma diagnosis fulfilling one of the following criteria (as per the american association for the study of liver diseases \[aasld\] guidelines, see appendix 5): 1. nodule in a cirrhotic or non-cirrhotic liver with a biopsy showing hcc; 2. nodule in cirrhotic liver where no biopsy is performed: * nodules between 1-2 cm in a cirrhotic liver with a typical coincidal vascular pattern of hcc (i.e. hypervascular with washout in the portal/venous phase) in two dynamic studies: either ct scan, contrast ultrasound or mri with contrast. * nodule larger than 2 cm in a cirrhotic liver with a typical vascular pattern of hcc on a dynamic imaging technique. please note: hcc in a non-cirrhotic liver can only be diagnosed with a biopsy showing hcc. * measurable disease according to modified recist (see appendix 7). * at least one treatment-naïve target lesion (treatment-naïve being defined as not having been treated with local therapy, such as surgery, radiation therapy, hepatic arterial embolisation, chemoembolisation, radio-frequency ablation or cryo-ablation). * barcelona clinic liver cancer (bclc) stage a, b or c (see appendix 6) (stage d is excluded). * child-pugh stage a (see appendix 8). * male or female aged 18 years or older. * adequate haematological parameters, as demonstrated by: * haemoglobin greater than or equal to 9.0 g/dl (si units: 5.6 mmol/l); * wbc greater than or equal to 3.0 x 109/l; * platelets greater than or equal to 75 x 109/l. * alt and ast ≤ 5 times the upper limit of normal. * bilirubin \< 2 mg/dl. * serum creatinine smaller than or equal to 1.5 mg/dl (si units: 132 µmol/l). * performance status ecog 0 or 1. * minimum life expectancy of 3 months at screening. * written informed consent given prior to any study specific procedures. exclusion criteria: * hcc amenable to curative treatment or transplantation. * history of other malignancies in the last 5 years (10 years in the case of breast cancer), except for adequately treated non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and carcinoma in situ of the cervix. * known history of or co-existing autoimmune disease. * known central nervous system (cns) metastases. * known history of human immunodeficiency virus (hiv). * any medical condition that, in the opinion of the investigator, may compromise the compliance of the patient to receive study treatment and follow study procedures. * treatment with any other imp within 4 weeks prior to cyclophosphamide administration at day -3. * known sensitivity to any components of cyclophosphamide, gv1001 or gm-csf. * concomitant treatment with the following within 4 weeks of pre-treatment with cyclophosphamide: * anti-tumour treatment (including radiotherapy, chemotherapy, immunotherapy, endocrine therapy, cytokines, interferons, protease inhibitors, and gene therapy) and vaccines. * chronic corticosteroids (inhaled and topical steroids are permitted including low dose steroids at non-immunosuppressive doses e.g. 15 mg prednisolone daily for up to 7 days). * herbal medicine either containing hypericum perforacum (e.g., st johns wort) or claiming to have anti-tumour effects (e.g., iscador). * pregnancy or lactation. * women of childbearing potential not using reliable and adequate contraceptive methods, defined as the use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; or women who are practising abstinence; or where the partner is sterile, for example a vasectomy. * unable for any other reason to comply with the protocol (treatment or assessments).

Keywords: advanced carcinoma, hepatocellular