Safety and efficacy trial of a RNActive®-derived prostate cancer vaccine in hormone refractory disease

• Conditions: patients with hormone-refractory prostate cancer (HRPC) with rising PSA; MedDRA version: 9.1Level: LLTClassification code 10062904Term: Hormone-refractory prostate cancer

• Registration Number: EUCTR2008-003967-37-DE
• Lead Sponsor: CureVac GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-21
• Last Update Posted: 26 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 50

Inclusion Criteria

1. Signed informed consent in accordance with GCP and local regulatory
requirements prior to trial participation
2. Male and age = 18 yrs (Phase I and II) and = 75 yrs (Phase II only)
3. Histologically confirmed diagnosis of adenocarcinoma of the prostate,
Gleason Score available
4. Patients must have been treated with hormonal therapy and may have been
treated with surgery and/ or radiation therapy
5. 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)
6. Presence of metastatic disease is acceptable
7. ECOG performance status of 0 to 1
8. Life expectancy > 12 months as assessed by the investigator
9. 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
10. Concomitant LH-RH therapy continuation is acceptable11. May have had local palliative radiotherapy for bone metastasis involving less
than 25% of bone marrow
12. 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
13. Patients of child-producing potential must agree to use contraception while
enrolled in the study and for one month after the last immunization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

The following are criteria for exclusion of patients from participating in the study:
1. Other histologic type of prostate cancer (transitional cell, small cell or
squamous cell cancer)
2. Symptomatic brain metastasis or leptomeningeal involvement
3. Patients having received or currently receiving chemo- or biological
therapy for prostate cancer
4. Symptomatic congestive heart failure (NYHA 3 and 4); unstable angina
pectoris; significant cardiac arrhythmia
5. Pulmonary disease causing dyspnea or fatigue during normal activity
6. History of seizures, encephalitis or multiple sclerosis
7. Inflammatory bowel disease e.g. Crohn’s disease or ulcerative colitis; active
diverticulitis
8. 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
9. Primary or secondary immune deficiency
10. History of allergy requiring medication
11. Active drug abuse or chronic alcoholism
12. Clinically significant active infections
13. Seropositive for HIV, HBV or HCV
14. History of other malignancies over the last 5 years (except basal cell
carcinoma of the skin)
15. Uncontrolled medical condition considered as high risk for the treatment with
an investigational drug including unstable diabetes mellitus, vena-cavasyndrome,
known ascites and/or pleural effusion, symptomatic pleural
effusion treated by puncture
16. Renal insufficiency requiring dialysis
17. Patients being committed to an institution by virtue of an order issued either
by the judicial or the administrative authorities.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase I part:<br>Determination of the recommended dose (RD) for exploration in the phase II part<br>Phase II part:<br>Assessment of safety of the trial regimen;Secondary Objective: Phase I part:<br>Assessment of safety of the trial regimen<br>Evaluation of induction of immune response<br><br>Phase II part:<br>Evaluation of induction of immune response<br>Assessment of anti-tumor activity;Primary end point(s): Phase I part:<br>Primary endpoint: occurrence of DLT before the week 5 visit in patients evaluablefor determination of RD<br>Phase II part:<br>Primary safety endpoints:<br>• incidence and severity of adverse events and laboratory abnormalities,<br>graded according to NCI-CTCAE version 3.0 criteria<br>• occurrence of Serious Adverse Events<br>• occurrence of treatment discontinuation due to adverse events<br>• incidence of treatment emergent autoimmune disease or development of<br>autoimmune antibodies