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Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CureVac GmbH
ClinicalTrials.gov Identifier:
NCT01817738
First received: February 8, 2013
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to determine whether the new RNActive-derived prostate cancer vaccine CV9104 prolongs survival in patients with asymptomatic or minimally symptomatic metastatic prostate cancer that is castrate resistant.


Condition Intervention Phase
Prostate Cancer
Biological: CV9104
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled, Phase I/II Trial of RNActive®-Derived Cancer Vaccine (CV9104) in Asymptomatic or Minimally Symptomatic Patients With Metastatic Castrate-refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by CureVac GmbH:

Primary Outcome Measures:
  • Phase I (Safety Lead-In): Occurence of dose-limiting toxicity (DLT) during the first 4 weeks of treatment (after administration of 3 vaccinations and after a 1 week observation period [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

    Safety Lead in Portion:

    Patients will receive CV9104 at a starting dose of 1920 µg in weeks 1, 2 and 3. Safety lead-in patients will be observed for DLTs until 1 week after Vaccination 3 (week 4). In case no DLTs will be observed vaccinations will continue in weeks 5, 7, 9, 12, 15, 18 and 24, then every 6 weeks for up to 12 months after the first vaccination and then every 3 months thereafter until one of the criteria for study treatment discontinuation is met


  • Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years. [ Time Frame: Overall survival will be assessed during the lifetime of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival from date of randomisation [ Time Frame: Every 3 months for up to 2 years ] [ Designated as safety issue: No ]
  • Progression free survival from start of first subsequent systemic therapy [ Time Frame: Every 6 months until 2 years ] [ Designated as safety issue: No ]
  • Percent change to maximal and to minimal PSA from baseline and before start of first subsequent systemic cancer therapy [ Time Frame: Every 3 months up to 2 years ] [ Designated as safety issue: No ]
  • Cellular and humoral immune response rate against the 6 antigens encoded by CV9104 [ Time Frame: Immune responses will be assessed at baseline ,in week 6 and week 24 after start of vaccination ] [ Designated as safety issue: No ]
  • Absolute change from baseline FACT P score and subscores [ Time Frame: Assessments at baseline, weeks 5,9,18,24 and every 3 months for up to 2 years ] [ Designated as safety issue: No ]
  • Absolute change from baseline EQ-5D score and pain sub-score [ Time Frame: Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 197
Study Start Date: August 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CV9104
CV9104 intradermal injection
Biological: CV9104
Intradermal injection of CV9104
Placebo Comparator: Placebo
Placebo intradermal injection
Biological: Placebo
Intradermal injection of placebo

Detailed Description:

The study is the first clinical study with the new prostate cancer vaccine CV9104. This vaccine is composed of 6 RNActive-based compounds, each encoding for an antigen that is overexpressed in prostate cancer compared to healthy tissues. RNActive-based vaccines are a novel class of vaccines based on messenger RNA.

The study is a double-blind randomized placebo-controlled phase I/II trial in men with asymptomatic- minimally symptomatic metastatic castrate-refractory prostate cancer.

The phase 1 (safety lead- in) part of the trial has the primary objective to assess the safety of CV9104 and to determine the dose for the randomized phase II part.

The primary objective of the phase II part is to compare overall survival in patients treated with CV9104 compared to patients treated with placebo.

  Eligibility

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

Key Inclusion Criteria:

  1. Male, age ≥18 years
  2. Histologically confirmed castrate refractory metastatic adenocarcinoma of the prostate with progressive disease after surgical castration or during androgen suppression therapy including a GNRH agonist or antagonist and after at least 1 additional anti-hormonal manipulation; and serum testosterone level of < 50 ng/dL or < 1.7 nmol/L

    Progression will be confirmed either

    • radiologically or
    • by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and a PSA > 2 ng/mL.
    • An antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy for at least 6 weeks.
  3. Metastatic disease confirmed by imaging
  4. ECOG performance status 0 or 1

Key Exclusion Criteria:

  1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
  2. Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
  3. Systemic treatment with immunosuppressive agents
  4. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
  5. History of or current autoimmune disorders
  6. Primary or secondary immune deficiency.
  7. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
  8. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to WHO criteria or uncontrolled hypertension at the time of enrolment (systolic blood pressure ≥ 180 mm Hg)´
  9. Previous chemotherapy for metastatic PCA.
  10. Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
  11. Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
  12. Presence of visceral metastases.
  13. History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).
  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: NCT01817738

  Show 48 Study Locations
Sponsors and Collaborators
CureVac GmbH
Investigators
Principal Investigator: Arnulf Stenzl, Prof. Dr. Universityhospital of Tübingen; Dept. of Urology
  More Information

Additional Information:
No publications provided

Responsible Party: CureVac GmbH
ClinicalTrials.gov Identifier: NCT01817738     History of Changes
Other Study ID Numbers: CV-9104-004
Study First Received: February 8, 2013
Last Updated: December 19, 2013
Health Authority: Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by CureVac GmbH:
Metastatic
Castrate-refractory

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014