Clinical trial NCT00831467: Safety and Efficacy Trial of a RNActive®-Derived Prostate Cancer Vaccine in Hormone Refractory Disease
Official title: Safety and Efficacy Trial of a RNActive®-Derived Prostate Cancer Vaccine in Hormone Refractory Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hormonal Refractory Prostate Cancer
Keywords: Hormonal refractory prostate cancer
RNA vaccine
Lead sponsor: CureVac
Sponsor class: INDUSTRY
First posted: 2009-01-29
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of a new vaccine in hormone refractory prostate cancer

Detailed description: Immunotherapy of prostate cancer is a promising approach for the treatment of advanced or recurrent forms of prostate cancer. Recently, immunotherapy of prostate cancer has been facilitated by the identification of a number of prostate specific antigens that are expressed in healthy and tumor prostate tissues. For prostatectomized patients, such antigens offer ideal targets for immunotherapy as they are only present in tumor but not in healthy tissue. The use of prostate specific antigens in a cancer vaccine is one attractive option for cancer immunotherapy.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation
* Male and age ≥ 18 years (Phase I and II) and ≤ 75 years (Phase II only)
* Histologically confirmed diagnosis of adenocarcinoma of the prostate, Gleason Score available
* Patients must have been treated with hormonal therapy and may have been treated with surgery and/ or radiation therapy
* Progressive disease as defined by hormone-refractoriness and rise in PSA:

Hormone-refractoriness: Defined by a rise in PSA and/or RECIST-based progression of evaluable lesions, and/or increased number of hotspots on a bone scan, while the patient has a castrated level of testosterone. This castrated level may have been obtained by orchiectomy, or LH-RH analog ± antiandrogen. Antiandrogen must be discontinued for at least 4 weeks before study entry to exclude a withdrawal effect.

Rise in PSA: Defined by a rise in PSA levels at three consecutive time points (PSA rise over nadir, separated by \> 1 week, PCWG2 criteria)

* Presence of metastatic disease is acceptable
* ECOG performance status of 0 to 1
* Life expectancy \> 12 months as assessed by the investigator
* Adequate organ function :

Bone marrow function: Hemoglobin ≥ 10 g/dL; Leukocytes ≥ 3000/µL; Lymphocytes ≥ 1000/µL; Absolute neutrophil count ≥ 1500/µL; Platelet count ≥ 100000/µL Hepatic: AST and ALT ≤ 2.5 times upper limit of normal (ULN); Bilirubin ≤ 1.5 ULN Renal: Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60mL/min

* Concomitant LH-RH therapy continuation is acceptable
* May have had local palliative radiotherapy for bone metastasis involving less than 25% of bone marrow
* Patients requiring bisphosphonates at the time of registration into the trial are eligible (therapy initiated at least 28 days prior to first study treatment administration) and must be continued at a constant level during the study period.
* Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization.

Exclusion Criteria:

* Other histologic type of prostate cancer (transitional cell, small cell or squamous cell cancer)
* Symptomatic brain metastasis or leptomeningeal involvement
* Patients having received or currently receiving chemo- or biological therapy for prostate cancer
* Symptomatic congestive heart failure (NYHA 3 and 4); unstable angina pectoris; significant cardiac arrhythmia
* Pulmonary disease causing dyspnea or fatigue during normal activity
* History of seizures, encephalitis or multiple sclerosis
* Inflammatory bowel disease e.g. Crohn's disease or ulcerative colitis; active diverticulitis
* Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy, (e.g. sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis or systemic vasculitis), excepting autoimmune thyroiditis with only thyroid hormone replacement and stable disease \> 1 year
* Primary or secondary immune deficiency
* History of allergy requiring medication
* Active drug abuse or chronic alcoholism
* Clinically significant active infections
* Seropositive for HIV, HBV or HCV
* History of other malignancies over the last 5 years (except basal cell carcinoma of the skin)
* Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, known ascites and/or pleural effusion, symptomatic pleural effusion treated by puncture
* Renal insufficiency requiring dialysis
* Patients being committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Primary outcomes:
measure: Determination of the recommended dose for exploration in the phase II part
timeFrame: 6-9 months
measure: Assessment of Safety of trial regimen
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Urologische Klinik
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Urologische Klinik u. Hochschulambulanz
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Urologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik und Poliklinik für Urologie, Uroonkologie und Kinderurologie
city: Frankfurt am Main
country: Germany
facility: Klinikum der JWG-Universität, Klinik für Urologie und Kinderurologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Abteilung Urologie
city: Lübeck
country: Germany
facility: UKSH Campus Lübeck, Klinik und Poliklinik fur Urologie
city: Mainz
country: Germany
facility: Johannes-Gutenberg-Universität Mainz, Urologische Klinik und Poliklinik
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, Urologische Klinik
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München, Urologische Klinik und Poliklinik
city: Tübingen
country: Germany
facility: Klinik für Urologie, Universitätsklinikum Tübingen
city: Milano
country: Italy
facility: Fondazione scientifica Istituto San Raffaele
Study officials:
affiliation: PMID: 19143027
name: Kurt Miller, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-Zrna S, Probst J, Kallen KJ. Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother. 2011 Jan;34(1):1-15. doi: 10.1097/CJI.0b013e3181f7dbe8.