Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01915524
Recruitment Status : Terminated (Slow recruitment in stratum 3: enrolled only 2 instead of 8 pts. within predicted time)
First Posted : August 5, 2013
Last Update Posted : August 5, 2016
Sponsor:
Information provided by (Responsible Party):
CureVac AG

Tracking Information
First Submitted Date  ICMJE July 18, 2013
First Posted Date  ICMJE August 5, 2013
Last Update Posted Date August 5, 2016
Study Start Date  ICMJE April 2013
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
Number of participants with treatment related >= grade 3 adverse events (AEs). [ Time Frame: up to 40 months ]
Events are graded by the investigator using the NCI CTCAE Scale (version 4.0) which provides a grading scale for each AE term. Grade 3 = Severe Grade 4 = Life-threatening or disabling Interim safety evaluations will be performed:
  • After treatment and observation of the first 6 patients until Day 43 in a given stratum. - If >= 2 out of 6 patients experience treatment-related >= grade 3 AEs, enrollment in that stratum will be suspended.
  • After the first 6 patients (enrolled in stratum 1 or 2) have received radiation of thoracic lesions and have been monitored for toxicity until Day 57:
    • If >= 2 out of 6 patients experience >= grade 3 radiation pneumonitis, radiation of thoracic lesions will be suspended for further patients.
    • For strata 1 and 2, CV9202 administration and radiation of thoracic lesions will be considered safe for further evaluation if ≤ 20% of patients experience a >= grade 3 radiation pneumonitis and no patients experience grade 4 radiation pneumonitis.
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
Number of participants with treatment related >= grade 3 adverse events (AEs). [ Time Frame: up to 24 months ]
Events were graded by the investigator using the NCI CTCAE Scale (version 4.0) which provides a grading scale for each AE term. Grade 3 = Severe Grade 4 = Life-threatening or disabling Interim safety evaluations will be performed:
  • After treatment and observation of the first 6 patients until Day 43 in a given stratum. - If >= 2 out of 6 patients experience treatment-related >= grade 3 AEs, enrollment in that stratum will be suspended.
  • After the first 6 patients (enrolled in stratum 1 or 2) have received radiation of thoracic lesions and have been monitored for toxicity until Day 57:
    • If >= 2 out of 6 patients experience >= grade 3 radiation pneumonitis, radiation of thoracic lesions will be suspended for further patients.
    • For strata 1 and 2, CV9202 administration and radiation of thoracic lesions will be considered safe for further evaluation if ≤ 20% of patients experience a >= grade 3 radiation pneumonitis and no patients experience grade 4 radiation pneumonitis.
Change History Complete list of historical versions of study NCT01915524 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
  • humoral and cellular immune responses against the 6 antigens encoded by CV9202. [ Time Frame: assessments at baseline, Day 19, Day 61 after start of study treatment ]
  • broadening of humoral immune responses (antigen spreading, i.e. change in serum antibody patterns) against a panel of tumor antigens not covered by the vaccine. [ Time Frame: Assessment at baseline, Day 19, Day 61 and 12 weeks, 24 weeks and 48 weeks after Day 57 ]
  • overall tumor response. [ Time Frame: At Screening and every 6 weeks during study treatment until progression up to 18 months after start of treatment of the last patient enrolled ]
  • progression free survival (PFS) and time to start of second-line treatment [ Time Frame: every 6 weeks up to 18 months after start of treatment of the last patient enrolled ]
  • response to second-line cancer treatment [ Time Frame: every 3 months after completion of study treatment until death, withdrawal of informed consent, or loss to follow-up or until up to 18 months after start of treatment of the last patient enrolled ]
  • overall survival (OS) from time of first vaccination. [ Time Frame: From first study treatment until time of death assessed up to 40 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
  • To assess humoral and cellular immune responses against the 6 antigens encoded by CV9202. [ Time Frame: assessments at baseline, Day 19, Day 61 after start of study treatment ]
  • To investigate broadening of humoral immune responses (antigen spreading, i.e. change in serum antibody patterns) against a panel of tumor antigens not covered by the vaccine. [ Time Frame: Assessment at baseline, Day 19, Day 61, every 12 weeks after Day 57 after start of study treatment ]
  • To investigate overall tumor response. [ Time Frame: At Screening and every 6 weeks during study treatment until progression up to an average of 6 months ]
  • To assess progression free survival (PFS)and time to start of second-line treatment [ Time Frame: every 6 weeks up to an average of 6 months ]
  • To assess response to second-line cancer treatment [ Time Frame: every 6 weeks after completion of study treatment for up to 18 months after enrollment of the last patient ]
  • To assess overall survival (OS) from time of first vaccination. [ Time Frame: From first study treatment until time of death assessed up to 36 months ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE An Exploratory, Open-label Phase Ib Study of RNActive®-Derived Cancer Vaccine and Local Radiation as Consolidation and Maintenance Treatment in Patients With Stage IV NSCLC and a Response or Stable Disease After First-line Chemotherapy or Therapy With an EGFR Tyrosine Kinase Inhibitor
Brief Summary The purpose of this study is to determine whether the new RNActive derived lung cancer vaccine CV9202 in combination with local radiation therapy is safe, tolerable and immunogenic for the consolidation and maintenance treatment of stage IV non small cell lung cancer (NSCLC) after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor.
Detailed Description

The Phase Ib study is the first clinical study with the new lung cancer vaccine CV9202. The vaccine is composed of 6 RNActive compounts, each encoding for a different antigen which is overexpressed in NSCLC compared to healthy tissue.

In order to enhance the immunogenic effect of the cancer vaccine, the study treatment will include local radiation (4 x 5 Gy), which is a well-established palliative radiation regimen that can be safely applied to metastatic lesions in the lung, bone, and soft tissue, and is well tolerated.

Patients will be enrolled into 3 strata based on histologic and molecular subtypes as follows:

Stratum 1: Patients with metastatic stage IV NSCLC and non-squamous histology, without activating epidermal growth factor receptor (EGFR) mutations, who have achieved partial response (PR) or stable disease (SD) after at least 4 cycles of platinum- and pemetrexed-based first-line chemotherapy, and an indication for maintenance therapy with pemetrexed.

Stratum 2: Patients with stage IV NSCLC and squamous cell histology, who achieved PR or SD after at least 4 cycles of platinum-based and non-platinum compound first-line chemotherapy.

Stratum 3: Patients with stage IV NSCLC and non-squamous histology, harboring an activating EGFR mutation, who have achieved PR after up to 6 months or SD after 3 - 6 months of treatment with an EGFR TKI.

In each patient, the vaccine will be administered until progression and the need to start a subsequent systemic second-line treatment, or occurrence of unacceptable toxicity requiring treatment discontinuation, whichever comes first.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Carcinoma
Intervention  ICMJE
  • Biological: CV9202
    Intradermal injection of CV9202
  • Radiation: local radiation
    Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week
Study Arms Experimental: CV9202 and local radiation

CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens.

local radiation (4x5 Gy)

Interventions:
  • Biological: CV9202
  • Radiation: local radiation
Publications *

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: April 10, 2015)
26
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2013)
36
Actual Study Completion Date July 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Patients >= 18 years of age with histologically or cytologically-confirmed stage IV NSCLC, and a confirmed EGFR mutation status in case of non-squamous cell histology

    • Stratum 1: Non-squamous NSCLC without activating EGFR mutation
    • Stratum 2: Squamous NSCLC
    • Stratum 3: Non-squamous NSCLC harboring an activating EGFR mutation
  2. PR or SD according to RECIST Version 1.1 after first-line therapy which should have consisted of:

    • Stratum 1: PR or SD after cisplatin or carboplatin and pemetrexed treatment (at least 4 cycles)
    • Stratum 2: PR or SD after cisplatin or carboplatin and a non-platinum compound treatment (at least 4 cycles)
    • Stratum 3: PR after up to 6 months or SD after at least 3 and up to 6 months of gefitinib or erlotinib treatment
  3. For patients in stratum 1, maintenance therapy with pemetrexed should be indicated as to the investigator's opinion
  4. Presence of at least one tumor lesion that is eligible for radiation with 4 x 5 GY, and at least one additional measurable tumor lesion according to RECIST Version 1.1.

    Tumor lesions eligible for radiation are:

    • Bone metastases
    • Lymph nodes in the paraclavicular, axillary or cervical regions
    • Skin or subcutaneous metastases
    • For patients in strata 1 and 2 only: Thoracic lesions (centrally located lung tumor, lymph nodes in the lung hilus or mediastinum)
  5. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 1

Key Exclusion Criteria:

  1. Previous active immunotherapy for NSCLC (including vaccination, therapy with anti-CTLA4 antibodies)
  2. Estimated life expectancy ≤ 3 months
  3. Need for immunosuppressive treatment including daily systemic steroid doses of ≥ 10 mg prednisone equivalent per day
  4. Active skin disease (e.g. atopic dermatitis) in the areas for vaccine injection (upper arms or thighs) not allowing intradermal injections into areas of healthy skin
  5. Concurrent or planned major surgery
  6. Prior splenectomy or prior allogeneic bone marrow transplantation
  7. History of pneumonitis
  8. Documented history or active autoimmune disorders with the exception of vitiligo, diabetes mellitus type 1 or autoimmune thyroiditis requiring hormone replacement only
  9. Primary or secondary immune deficiency
  10. Allergies to any components of the study drug including allergy to protamine hydrochloride (e.g. allergy to protamine-containing insulin) or fish allergy
  11. Seropositive for HIV, HBV, HCV or any other infection requiring anti-infection therapy
  12. For patients in stratum 3: persisting >= grade 3 skin rash at time of enrollment
  13. Known brain metastases with the exception of stable metastases being treated with stereotactic radiation or surgery)

    **Local German Amendment: 13. Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement

  14. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable diabetes mellitus, vena-cava-syndrome, uncontrolled pleural effusion, pericardial effusion, symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris/myocardial infarction within the previous 6 months, significant cardiac arrhythmia, history of stroke or transient ischemic attack within the previous 6 months, severe hypertension according to WHO criteria, and uncontrolled systolic blood pressure ≥ 180 mmHg at the time of enrollment
  15. For patients planned to undergo radiation of thoracic lesions: inadequate lung function dependent on the intended tumor volume and location to be irradiated (to be assessed by the radio oncologist)
  16. History of encephalitis or multiple sclerosis
  17. Active inflammatory conditions such as inflammatory bowel disease
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01915524
Other Study ID Numbers  ICMJE CV-9202-006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party CureVac AG
Study Sponsor  ICMJE CureVac AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alfred Zippelius, Prof. Dr. University Hospital Basel, Clinic for Medical Oncology
PRS Account CureVac AG
Verification Date August 2016

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