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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CureVac GmbH
ClinicalTrials.gov Identifier:
NCT00923312
First received: June 16, 2009
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

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).


Condition Intervention Phase
Non Small Cell Lung Cancer
Biological: CV9201
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy Phase I/IIa Trial of an RNActive®-Derived Cancer Vaccine in Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by CureVac GmbH:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Phase II: Assessment of safety and tolerability of the treatment regimen [ Time Frame: Complete duration of Phase II ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 33
Study Start Date: May 2009
Estimated Study Completion Date: February 2014
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CV9201
CV9201 is composed of five formulated mRNAs (drug product components) encoding antigens that are overexpressed or exclusively expressed in NSCLC cells.
Biological: CV9201
CV9201 is a vaccine consisting of five drug product components. Treatment will be administered on 5 timepoints.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00923312

Locations
Germany
RWTH Aachen
Aachen, Germany, 52074
Medizinische Klinik III, Universitätsklinikum Bonn
Bonn, Germany, 53111
Medizinische Klinik V, Klinikum Darmstadt
Darmstadt, Germany, 64283
Medizinische Klinik I, Universitätsklinikum Dresden
Dresden, Germany, 01304
Nordwest Krankenhaus
Frankfurt, Germany, 60488
Krankenhaus Großhansdorf
Großhansdorf, Germany, 22927
Universitätsklinikum Hamburg Eppendorf, Medizinische Klinik II
Hamburg, Germany, 20246
Thoraxklinik am Universitätsklinikum Heidelberg
Heidelberg, Germany, 69126
Universitätsklinikum des Saarlandes
Homburg, Germany, 66421
III. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz
Mainz, Germany, 55131
III. Medizinische Klinik, Klinikum rechts der Isar
München, Germany, 81675
Medizinische Klinik II, Universität Tübingen
Tübingen, Germany, 72074
Switzerland
UniversitätsSpital Basel
Basel, Switzerland, 4031
UniversitätsSpital Zürich
Zürich, Switzerland, 8091
Sponsors and Collaborators
CureVac GmbH
Investigators
Principal Investigator: Alexander Knuth, Prof. Dr. UniversitätsSpital Zürich
  More Information

Additional Information:
No publications provided by CureVac GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: CureVac GmbH
ClinicalTrials.gov Identifier: NCT00923312     History of Changes
Other Study ID Numbers: CV-9201-003
Study First Received: June 16, 2009
Last Updated: October 4, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014