Asymptomatic or minimally symptomatic, chemo-naive mCRPC patients
Conditions
Interventions
Product Name: Tumor antigen peptide-loaded myeloid dendritic cell product
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Blood DC loaded with tumor peptides
Other descriptive name:
Sponsors
Radboud University Medical Centre Nijmegen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria All patients: • Men = 18 years of age and older with confirmed (histologically or cytologically) adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features • HLA-A2.1 positive • Asymptomatic or minimally symptomatic mCRPC • Metastatic castrate-resistant disease defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy: o PSA progression defined by PCWG2 criteria by a minimum of two rising PSA levels with an interval of at least 1 week between each determination o Progression of nodal metastases defined by RECIST version 1.1 criteria or progression on successive MRLs o Bone disease progression defined by two or more new lesions on bone scan as described in PCWG2 criteria • Maintenance of castrate circumstances: o Ongoing primary androgen deprivation therapy (GnRH agonist or antagonist) o Serum testosterone level equal to or less than 1.73 nmol/L (50 ng/dL) • PSA value equal to or more than 2 ng/ml • Absence of visceral metastases, malignant ascites or pleural effusion • Clinical absence of brain metastases • Inclusion within three months after the moment of manifestation of progressive disease as defined above • Chemotherapy naïve • Life expectancy = 3 months • WHO/ECOG performance status 0-1 (Karnofsky index 100-70) • WBC >2.0x109/l, neutrophils >1.5x109/L lymphocytes >0.8x109/L, platelets >100x109/L, hemoglobin >5,6 mmol/L (9.0 g/dL), serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: Exclusion criteria • Hypercalcemia • History of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma • Known allergy to shell fish • Heart failure (NYHA class III/IV) • Serious active infections • Active hepatitis B, C or HIV infection • Active syphilis infection • Autoimmune diseases (exception: vitiligo is permitted) • Organ allografts • An uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation • Previous treatment with sipuleucel-T,PROSTVAC, GVAX, chemotherapy, ipilimumab or denosumab (previous treatment with abiraterone acetate or enzalutamide is permitted) • Prior radiotherapy within 4 weeks prior to planned vaccination or presence of treatment-related toxicity • Continued use of non-steroidal anti-inflammatory drugs • Concurrent use of systemic corticosteroids > 10 mg daily prednisone equivalent • Requirement of opiate use for cancer-related pain (at screening) • Any serious clinical condition that may interfere with the safe administration of DC vaccinations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show immunologic efficacy of tumor-peptide loaded natural DC in mCRPC patients;Secondary Objective: As secondary objectives we aim to demonstrate that natural DC vaccinations are safe, feasible and clinically effective. Also the therapy effect on quality of life will be studied. ;Primary end point(s): The primary objective of this Radboudumc initiated study is to evaluate the immunogenicity of tumor-peptide loaded natural DC in mCRPC patients. Immunogenicity is defined as the antitumor immune response induced in prostate cancer patients. Therefore, immunomonitoring will be performed that includes: a) Functional response and tetramer analysis of delayed-type hypersensitivity (DTH)-infiltrating T cells against tumor peptides. The occurrence and magnitude of the response will be compared. b) Type I IFN gene expression in PBMC shortly after vaccination. The occurrence and magnitude of the type I IFN response in patients will be compared. c) Proliferative, effector cytokine- and humoral responses to keyhole limpet hemocyanin (KLH), a immunogenic protein providing T cell help. ;Timepoint(s) of evaluation of this end point: a) After every round of natural DC vaccinations a DTH and biopsies will be performed for functional response and tetramer analysis. This is approximately 5 weeks after the first vaccination. b) 4 hours and 24 hours after each vaccination c) at the following time points: apheresis, before second vaccination, before third vaccination, before DTH, and 6 weeks after DTH | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives are the safety and feasibility of vaccinations, the quality of life and the clinical efficacy of mDC and pDC vaccinations. Clinical efficacy is defined as the proportion of subjects who remain 6 months free of: radiological progression, PSA progression, progression free survival, opiate use for cancer-related pain, a skeletal-related event (SRE), decline in WHO/ECOG performance score by = 1 point and initiation of cytotoxic chemotherapy. Overall survival will be verified by gathering the date of death using the electronic hospital records or the electronic records of the general practitioner. Safety will be evaluated by adverse events, WHO performance status, physical examinations and laboratory tests until 6 weeks following the last study treatment. Toxicity will be assessed according to the CTCAE version 4.03. To assess the quality of life four validated questionnaires will be collected every 6 weeks. These screening tools are validated in the Dutch language.;Timepoint(s) of evaluation of this end point: Safety: during the whole trial Feasibility: during the whole trial Quality of life questionnaires: every 6 weeks Clinical efficacy: imaging (before treatment, 6 weeks after the third vaccination, before second round), PSA (every 6 weeks). In case of stable disease or remission of disease also during the second round of vaccinations, the third round of vaccinations, and during the follow-up of 1 year thereafter, imaging and PSA measurement will be performed. Existance of cancer-related pain/ WHO performance score and start of chemotherapy: during the whole trial. | — |
Countries
Netherlands
Contacts
Public ContactRadboudumc
Radboud University Medical Centre Nijmegen
Outcome results
None listed