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Trial record 75 of 2089 for:    cancer vaccine

Trial of an RNActive®-Derived Cancer Vaccine in Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT00923312
Recruitment Status : Completed
First Posted : June 18, 2009
Last Update Posted : March 20, 2018
Sponsor:
Information provided by (Responsible Party):
CureVac AG

Tracking Information
First Submitted Date  ICMJE June 16, 2009
First Posted Date  ICMJE June 18, 2009
Last Update Posted Date March 20, 2018
Study Start Date  ICMJE May 2009
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2009)
  • Phase I: Determination of the recommended dose (RD) for exploration in the phase IIa part of the study [ Time Frame: During the first 2-3 month of Phase I ]
  • Phase II: Assessment of safety and tolerability of the treatment regimen [ Time Frame: Complete duration of Phase II ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2009)
  • Phase I: Assessment of safety of the treatment regimen [ Time Frame: During complete duration of Phase I ]
  • Phase I: Evaluation of induction of immune response [ Time Frame: During complete duration of Phase I ]
  • Phase I: Assessment of anti-tumor activity [ Time Frame: During complete duration of Phase I ]
  • Phase II: Evaluation of induction of immune response [ Time Frame: During complete duration of Phase II ]
  • Phase II: Assessment of anti-tumor activity [ Time Frame: During complete duration of Phase II ]
  • Phase II: Correlation between tumor-associated antigen (TAA) expression on tumor specimens (if available) and survival/ progression/ immunological response [ Time Frame: During complete duration of Phase II ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of an RNActive®-Derived Cancer Vaccine in Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE Safety and Efficacy Phase I/IIa Trial of an RNActive®-Derived Cancer Vaccine in Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)
Brief Summary

This is a phase I/IIa open, uncontrolled, international, prospective clinical trial, in an out-patient setting, in patients with stage IIIB/IV NSCLC.

The phase I part of the study consists of a dose escalation phase, in which the recommended dose (RD) for the phase IIa part of the study will be established based on the incidence of dose-limiting toxicities (DLT). In the phase IIa part of the study, additional patients will be included at the RD, to confirm the safety and explore the activity of that dose.

This study will take place in Switzerland (2 sites) and Germany (11 sites).

Detailed Description

Medical Need:

Lung cancer is the leading cause of cancer mortality in developed countries; about 87% of lung cancers are of the NSCLC type. Patients with more advanced but non-metastatic disease (IIIA or IIIB) usually undergo chemotherapy and/or radiation therapy, with or without secondary surgical resection. Patients with progression after chemotherapy and/or radiotherapy may receive second-line treatment with targeted therapies. Despite these aggressive treatments, only about 5% of patients with metastatic disease survive for 5 or more years. Given these dismal statistics, it is clear that new therapeutic approaches for treatment of NSCLC are urgently needed.

Potential Benefits:

CV9201 is an mRNA-based vaccine for the treatment of human NSCLC that is based on CureVac's RNActive® technology.

As an mRNA-based vaccine, CV9201 features several advantages over other approaches: it is highly specific, there is no restriction to the patient's MHC genotype, and it does not need to cross the nuclear membrane to be active. Finally, in the absence of reverse transcriptase, RNA can not be integrated into the genome.

For the planned first-in-man study, CV9201 will be administered in 5 doses. The phase I part of this phase I/IIa study is a dose finding study, to determine the RD for the phase IIa part.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE Biological: CV9201
CV9201 is a vaccine consisting of five drug product components. Treatment will be administered on 5 timepoints.
Study Arms  ICMJE Experimental: CV9201
CV9201 is composed of five formulated mRNAs (drug product components) encoding antigens that are overexpressed or exclusively expressed in NSCLC cells.
Intervention: Biological: CV9201
Publications * Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkić-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 11, 2014)
46
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2009)
30
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female and age ≥ 18 yrs and ≤ 75
  2. Histologically or cytologically confirmed and documented stage IIIB /IV NSCLC
  3. Documented stable disease or objective response according to RECIST criteria after initial chemotherapy or chemo-radiotherapy for advanced, unresectable disease:

    • Patients must have received a minimum of two cycles of standard chemotherapy, and adequate and effective radiotherapy if used in conjunction with chemotherapy (sequentially or concomitantly). Prophylactic brain radiation is allowed.
    • Surgery, radiotherapy and/ or chemotherapy can have been previously administered for non-advanced disease.
    • All therapies must be completed 4 weeks before start of study treatment.
  4. Performance status: Eastern Cooperative Oncology Group (ECOG) 0 - 1
  5. Life expectancy > 6 months as assessed by the investigator
  6. Adequate organ function:

    • Bone marrow function: hemoglobin ≥ 100 g/L; 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 ≥ 100 x 109/L
    • Hepatic: aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 x ULN if hepatic metastases present); bilirubin ≤ 1.5 x ULN
    • Renal: Creatinine ≤ 2 mg/ dL and creatinine clearance ≥ 45 mL/ min
  7. Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization
  8. Written informed consent must be obtained prior to conducting any study-specific procedures.

Exclusion Criteria:

  1. History of anti-cancer therapy for advanced disease other than initial chemotherapy or chemo-radiotherapy or surgery
  2. Immunotherapy within 4 weeks prior to study enrollment, including cytokines such as G-CSF, GM-CSF or interferons
  3. Treatment with investigational anti-cancer agents during initial therapy for advanced disease or any investigational agents within 4 weeks prior to study enrollment
  4. Concurrent anti-tumor therapy or concurrent immunotherapy such as lectins, unspecific immunostimulants, etc.
  5. Previous anti-cancer immunotherapy comprising RNA-transfected dendritic cells or DNA vaccines targeting any tumor-associated antigens
  6. Concurrent systemic steroids except topical (inhaled, topical, nasal) for the last 28 days, except replacement therapy
  7. Concurrent major surgery or planned surgery
  8. Prior splenectomy
  9. 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
  10. Primary or secondary immune deficiency
  11. Active allergy requiring continuous medication or active infections requiring anti-infectious therapy
  12. Seropositive for HIV, HBV or HCV
  13. History of other malignancies over the last 5 years (except basal cell carcinoma of the skin or carcinoma in situ of the cervix)
  14. 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 uncontrolled pleural effusion.
  15. Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement
  16. Symptomatic congestive heart failure (NYHA 3 and 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, history of stroke or transient ischemic attack
  17. History of seizures, encephalitis or multiple sclerosis
  18. Gastric ulcer or inflammatory bowel disease or Crohn's disease or ulcerative colitis; no active diverticulitis
  19. Active drug abuse or chronic alcoholism
  20. Patients being committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00923312
Other Study ID Numbers  ICMJE CV-9201-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CureVac AG
Study Sponsor  ICMJE CureVac AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alexander Knuth, Prof. Dr. Universitätsspital Zürich
PRS Account CureVac AG
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP