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An Open Label Randomised Trial of RNActive® Cancer Vaccine in High Risk and Intermediate Risk Patients With Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by CureVac GmbH
Sponsor:
Information provided by (Responsible Party):
CureVac GmbH
ClinicalTrials.gov Identifier:
NCT02140138
First received: April 7, 2014
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the induction of immune responses against CV9104 administered by conventional intradermal injection or with a needle-free intradermal injection device and to assess the safety and tolerability of CV9104 administered by conventional intradermal injection versus injection with a needle-free intradermal injection device versus no injection.


Condition Intervention Phase
Prostate Carcinoma
Biological: CV9104
Device: needle free injection device (TropisTM)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Randomised Phase II Trial of RNActive® Cancer Vaccine (CV9104) in High Risk and Intermediate Risk Patients With Prostate Cancer

Resource links provided by NLM:


Further study details as provided by CureVac GmbH:

Primary Outcome Measures:
  • Induction of antigen-specific cellular and humoral immune response to the vaccine antigens. [ Time Frame: Up to one week before the date of surgery. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of adverse device effects, adverse events and laboratory abnormalities, graded according to NCI-CTCAE version 4.0 criteria [ Time Frame: From ICF signature till end of study (max. up to week 20 after first study treatment in arm A and B and up to week 26 after first study treatment in arm C) ] [ Designated as safety issue: Yes ]
  • Occurrence of serious adverse events [ Time Frame: From ICF signature till end of study (max. up to week 20 after first study treatment in arm A and B and up to week 26 after first study treatment in arm C) ] [ Designated as safety issue: Yes ]
  • Occurrence of treatment discontinuation due to adverse events [ Time Frame: From time of first to last study treatment ] [ Designated as safety issue: Yes ]
  • Change in PSA serum levels during the presurgical period and, in patients receiving postsurgical vaccinations, change in PSA during the postsurgical period [ Time Frame: At screening, at baseline (week 1), at the last presurgical visit (week 6 in arm A and B, week 3-6 in arm C), at the first postsurgical visit (8 weeks after surgery) and at the end of study (max. up to week 21 in arm A and B and up to week 27 in arm C) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Assessment of immune cell infiltration, and gene expression profiles in prostatectomy tissue samples [ Time Frame: tissue collection at prostatectomy (week 6-7 in arm A and B, week 4-7 in arm C) ] [ Designated as safety issue: No ]
  • Assessment of immune parameters and biomarkers in blood and exprimate urine [ Time Frame: At baseline (week 1), at the last presurgical visit (week 6 in arm A and B, week 3-6 in arm C), at the first post surgical visit (8 weeks after surgery; blood only) and in week 13 after surgery (in arm C, receiving vaccinations after surgery). ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (i.d. vaccinations with needle free injecton device)

Duration: Patients in Arm A will receive a total of 4 vaccinations with CV9104 in weeks 1, 2, 3 and 5. These patients will undergo radical prostatectomy at least 1 week but not later than 2 weeks after the 4th vaccination (week 6 or 7). After surgery high risk patients will be offered to receive 2 additional vaccinations with CV9104 at week 8 and 10 post surgery.

Administration: At each vaccination visit each of the 6 components of CV9104 vaccine will be injected individually, divided in two separate intradermal injections. These 12 Injections will be distributed over the 4 limbs (3 injections in each upper arm and thigh).

Administration site: Skin of the lateral parts of the upper arms (over the deltoid regions) and the lateral part of the thighs.

Dose: 2 x 80 μg mRNA per injection (2 x 100 μL), equals 160 μg mRNA per RNActive® drug product component

Biological: CV9104 Device: needle free injection device (TropisTM)
Experimental: Arm B (i.d. vaccination by conventional injection)

Duration: Patients in Arm B will receive a total of 4 vaccinations with CV9104 in weeks 1, 2, 3 and 5. These patients will undergo radical prostatectomy at least 1 week but not later than 2 weeks after the 4th vaccination (week 6 or 7). After surgery high risk patients will be offered to receive 2 additional vaccinations with CV9104 at week 8 and 10 post surgery.

Administration: At each vaccination visit each of the 6 components of CV9104 vaccine will be injected individually, divided in two separate intradermal injections. These 12 Injections will be distributed over the 4 limbs (3 injections in each upper arm and thigh).

Administration site: Skin of the medial part of the upper arms and thigh

Dose: 2 x 160 μg mRNA per injection (2 x 200 μL), equals 320 μg mRNA per RNActive® drug product component

Biological: CV9104
Arm C (i.d. vaccination with needle free injection device)

Duration: Patients in Arm C will receive no vaccination before radical prostatectomy. After surgery high risk patients will be offered to receive 6 vaccinations with CV9104 at week 8, 9, 10, 12, 14 and 16 after surgery.

Administration: At each vaccination visit each of the 6 components of CV9104 vaccine will be injected individually, divided in two separate intradermal injections. These 12 Injections will be distributed over the 4 limbs (3 injections in each upper arm and thigh).

Administration site: Skin of the lateral parts of the upper arms (over the deltoid regions) and the lateral part of the thighs.

Dose: 2 x 80 μg mRNA per injection (2 x 100 μL), equals 160 μg mRNA per RNActive® drug product component

Biological: CV9104 Device: needle free injection device (TropisTM)

Detailed Description:

This study is the second clinical trial of the RNActive® vaccine. It is composed of 6 RNActive® drug product components, coding for 6 antigens that are overexpressed in PCA compared to healthy tissue. Each of the 6 prostate specific antigens that are encoded by CV9104 are capable of inducing adaptive immunity.

Needle-free injection systems, like the TropisTM device for i.d. injection, overcome the disadvantages related to needle- and syringe-based i.d. injections. TropisTM is currently used in different vaccine clinical trials around the world. The use of TropisTM for i.d. delivery of CV9104 has been approved by BfArM.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male aged ≥18 years
  2. Histologically confirmed localised adenocarcinoma of the prostate confirmed in at least 3 biopsies (out of at least 8 prostate biopsies) with at least 50% tumor infiltration in at least one of these biopsies and with at least one of the following criteria for intermediate to high risk disease:

    • Gleason Score 7-10
    • Serum PSA > 10 ng/mL
    • cT2b-c / cT3a without tumor fixation to adjacent organs

    but no more than one of the following criteria for high risk disease:

    • Gleason score of 8-10 OR
    • Serum PSA > 20 ng/mL OR
    • cT3a without tumor fixation to adjacent organs
  3. Absence of very high risk or metastatic disease (i.e. cT3b-T4 N0 or any T, N1 or M1) confirmed by EITHER CT or MRI of the abdomen and pelvis (in patients with a Gleason score ≥ 8 or a clinical stage T3) and bone scintigraphy (in patients with a PSA of ≥ 10 ng/mL, a Gleason score ≥ 8, a clinical stage T3 or bone pain or other symptoms of metastatic disease)
  4. Patient is physically fit and eligible for radical prostatectomy based on best clinical evidence and has already decided to undergo radical prostatectomy after discussion of potential alternative treatment options.
  5. ECOG 0 or 1
  6. No prior treatment for prostate cancer including prior surgery (including TURP), pelvic lymph node dissection, radiation therapy, antihormonal therapy or chemotherapy
  7. Adequate organ function:

    • Bone marrow function: hemoglobin ≥ 12 g/dL; white blood cell count (WBC) ≥ 3.0 x 109/L; lymphocyte count ≥ 1.0 x 109/L; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 150 x 109/L
    • Hepatic: AST, ALT and GGT ≤ 2.5 times upper limit of normal (ULN); bilirubin ≤ 1.5 x ULN
    • Renal: creatinine ≤ 2 mg/dL and creatinine clearance ≥ 45 mL/min/1.73 m2
  8. Fertile men and their female partners must use a highly effective method of contraception resulting in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Those methods include implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs) or abstinence. The contraception should be applied from enrollment until 4 weeks after the last vaccination.
  9. Written informed consent must be obtained prior to conducting any study-specific procedures.

Exclusion Criteria:

  1. Concurrent treatment with systemic steroids or other immunosuppressive agents [except topical (inhaled, topical, nasal) and replacement therapy for adrenal insufficiency] should be strictly avoided throughout the study, concomitant treatment with immunomodulating agents including herbal remedies (e.g. mistletoe extract) has to be avoided during study treatment and must be discontinued at least 28 days prior to the start of treatment
  2. Previous therapies with investigational anticancer agents including cancer vaccines or other cancer immunotherapies
  3. Prior splenectomy
  4. Prior allogeneic bone marrow transplant
  5. History of autoimmune disorders such as sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis or systemic vasculitis (except autoimmune thyroiditis with only thyroid hormone replacement and stable disease > 1 year)
  6. Primary or secondary immune deficiency
  7. Seropositive for HIV, HBV (except after Hep B vaccination) or HCV infection
  8. History of other malignancies over the last 5 years (except adequately treated basal cell or squamous cell carcinoma of the skin)
  9. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, symptomatic congestive heart failure (NYHA 3 and 4); coronary heart disease with unstable angina pectoris, history of myocardial infarction, or coronary artery intervention (PTCA, stenting) within 6 months prior to enrolment; significant cardiac arrhythmia, history of stroke or transient ischemic attack. Severe hypertension according to WHO criteria or systolic blood pressure ≥ 180 mmHg at the time of enrolment.
  10. History of seizures, encephalitis or multiple sclerosis
  11. History of inflammatory bowel disease or Crohn´s disease or ulcerative colitis
  12. Active drug abuse or chronic alcoholism
  13. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection preventing the i.d. administration of study product into areas of healthy skin
  14. Allergies to any component of the study drug including known allergy to protamine sulphate (e.g. allergy to protamine containing insulins) or fish allergy.
  15. Prior vasectomy
  16. Known type I allergy to β-lactam antibiotics
  17. Active infections (including acute prostatitis) requiring anti-infectious therapy at the time of enrolment: leucocytosis ≥ 9000/μL; CRP elevation ≥ 2.5 times upper limit of normal or leucocyturia of ≥ 75 cells/μl (equals ≥ grade 2+ on two consecutive Combur® urinalysis specimen)
  18. Uncontrolled urinary retention or hydronephrosis
  19. Inability to provide informed consent due to mental impairment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02140138

Contacts
Contact: Tobias Seibel, Dr. +49 69 7680 587 ext 0 clinicaltrials@curevac.com

Locations
Germany
Klinik für Urologie, Universitätsklinikum Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Arnulf Stenzl, Prof. Dr. med.    +49 7071 2986000    urologie@med.uni-tuebingen.de   
Principal Investigator: Arnulf Stenzl, Prof. Dr. med.         
Sponsors and Collaborators
CureVac GmbH
Investigators
Principal Investigator: Arnulf Stenzl, Prof. Dr. med. Klinik für Urologie, Universitätsklinikum Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany
Study Director: Ulrike Gnad-Vogt, Dr. CureVac GmbH, Schumannstr. 27, 60325 Frankfurt, Germany
  More Information

No publications provided

Responsible Party: CureVac GmbH
ClinicalTrials.gov Identifier: NCT02140138     History of Changes
Other Study ID Numbers: CV-9104-007, 2013-004489-32
Study First Received: April 7, 2014
Last Updated: May 15, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Carcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 28, 2014