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

NCT02140138 | Terminated Phase 2

• 2 other identifiers: CV-9104-0072013-004489-32
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

• Induction of antigen-specific cellular and humoral immune response to the vaccine antigens.

  Up to one week before the date of surgery.

Secondary Outcomes (4)

• Incidence and severity of adverse device effects, adverse events and laboratory abnormalities, graded according to NCI-CTCAE version 4.0 criteria

  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)

• Occurrence of serious adverse events

  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)

• Occurrence of treatment discontinuation due to adverse events

  From time of first to last study treatment

• Change in PSA serum levels during the presurgical period and, in patients receiving postsurgical vaccinations, change in PSA during the postsurgical period

  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)

Other Outcomes (2)

• Assessment of immune cell infiltration, and gene expression profiles in prostatectomy tissue samples.

  tissue collection at prostatectomy (week 6-7 in arm A and B, week 4-7 in arm C)

• Assessment of immune parameters and biomarkers in blood and exprimate urine

  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)

Study Arms (3)

Arm A (i.d. vaccinations with needle free injection device)

EXPERIMENTAL

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 or very 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 (Tropis®)

Arm B (i.d. vaccination by conventional injection)

EXPERIMENTAL

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 or very 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)

OTHER

Duration: Patients in Arm C will receive no vaccination before radical prostatectomy. After surgery high risk or very 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 (Tropis®)

Interventions

CV9104 BIOLOGICAL

Arm A (i.d. vaccinations with needle free injection device); Arm B (i.d. vaccination by conventional injection); Arm C (i.d. vaccination with needle free injection device)

needle free injection device (Tropis®) DEVICE

Arm A (i.d. vaccinations with needle free injection device); Arm C (i.d. vaccination with needle free injection device)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged ≥18 years
• Histologically confirmed adenocarcinoma of the prostate 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
• 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)
• 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.
• ECOG 0 or 1
• No prior treatment for prostate cancer including prior surgery (including TURP), pelvic lymph node dissection, radiation therapy, antihormonal therapy or chemotherapy
• 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
• 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.
• Written informed consent must be obtained prior to conducting any study-specific procedures.

You may not qualify if:

• 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
• Previous therapies with investigational anticancer agents including cancer vaccines or other cancer immunotherapies
• Prior splenectomy
• Prior allogeneic bone marrow transplant
• 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)
• Primary or secondary immune deficiency
• Seropositive for HIV, HBV (except after Hep B vaccination) or HCV infection
• History of other malignancies over the last 5 years (except adequately treated basal cell or squamous cell carcinoma of the skin)
• 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.
• History of seizures, encephalitis or multiple sclerosis
• History of inflammatory bowel disease or Crohn´s disease or ulcerative colitis
• Active drug abuse or chronic alcoholism
• 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
• Allergies to any component of the study drug including known allergy to protamine sulphate (e.g. allergy to protamine containing insulins) or fish allergy.
• Prior vasectomy

Sponsors & Collaborators

• CureVac: lead

Study Sites (3)

Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Klinik für Urologie, Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Klinikum rechts der Isar, Urologische Klinik und Poliklinik der Technischen Universität München

München, Bavaria, 81675, Germany

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Arnulf Stenzl, Prof. Dr. med.

  Klinik für Urologie, Universitätsklinikum Tübingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: May 16, 2014
• Study Start: June 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 13, 2016

Record last verified: 2016-06

Locations

DE (3)