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

NCT00923312 | Completed Phase 1 DMC

• 1 other identifier: CV-9201-003
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 14

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).

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Determination of the recommended dose (RD) for exploration in the phase IIa part of the study

  During the first 2-3 month of Phase I

• Phase II: Assessment of safety and tolerability of the treatment regimen

  Complete duration of Phase II

Study Arms (1)

CV9201

EXPERIMENTAL

CV9201 is composed of five formulated mRNAs (drug product components) encoding antigens that are overexpressed or exclusively expressed in NSCLC cells.

Biological: CV9201

Interventions

CV9201 BIOLOGICAL

CV9201 is a vaccine consisting of five drug product components. Treatment will be administered on 5 timepoints.

CV9201

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female and age ≥ 18 yrs and ≤ 75
• Histologically or cytologically confirmed and documented stage IIIB /IV NSCLC
• 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.
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0 - 1
• Life expectancy \> 6 months as assessed by the investigator
• 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
• Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization
• Written informed consent must be obtained prior to conducting any study-specific procedures.

You may not qualify if:

• History of anti-cancer therapy for advanced disease other than initial chemotherapy or chemo-radiotherapy or surgery
• Immunotherapy within 4 weeks prior to study enrollment, including cytokines such as G-CSF, GM-CSF or interferons
• Treatment with investigational anti-cancer agents during initial therapy for advanced disease or any investigational agents within 4 weeks prior to study enrollment
• Concurrent anti-tumor therapy or concurrent immunotherapy such as lectins, unspecific immunostimulants, etc.
• Previous anti-cancer immunotherapy comprising RNA-transfected dendritic cells or DNA vaccines targeting any tumor-associated antigens
• Concurrent systemic steroids except topical (inhaled, topical, nasal) for the last 28 days, except replacement therapy
• Concurrent major surgery or planned surgery
• Prior splenectomy
• 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
• Primary or secondary immune deficiency
• Active allergy requiring continuous medication or active infections requiring anti-infectious therapy
• Seropositive for HIV, HBV or HCV
• History of other malignancies over the last 5 years (except basal cell carcinoma of the skin or carcinoma in situ of the cervix)
• 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.
• Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement

Sponsors & Collaborators

• CureVac: lead

Study Sites (14)

RWTH Aachen

Aachen, 52074, Germany

Location

Medizinische Klinik III, Universitätsklinikum Bonn

Bonn, 53111, Germany

Location

Medizinische Klinik V, Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

Medizinische Klinik I, Universitätsklinikum Dresden

Dresden, 01304, Germany

Location

Nordwest Krankenhaus

Frankfurt, 60488, Germany

Location

Krankenhaus Großhansdorf

Großhansdorf, 22927, Germany

Location

Universitätsklinikum Hamburg Eppendorf, Medizinische Klinik II

Hamburg, 20246, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

III. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

III. Medizinische Klinik, Klinikum rechts der Isar

München, 81675, Germany

Location

Medizinische Klinik II, Universität Tübingen

Tübingen, 72074, Germany

Location

UniversitätsSpital Basel

Basel, 4031, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-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.

  PMID: 21150709 DERIVED

Related Links

• Homepage Sponsor

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alexander Knuth, Prof. Dr.

  Universitätsspital Zürich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2009
• First Posted: June 18, 2009
• Study Start: May 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: May 1, 2014
• Last Updated: March 20, 2018

Record last verified: 2013-10

Locations

DE (12); CH (2)