Trial record 3 of 6 for:    curevac

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by CureVac GmbH
Sponsor:
Information provided by (Responsible Party):
CureVac GmbH
ClinicalTrials.gov Identifier:
NCT01915524
First received: July 18, 2013
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Carcinoma
Biological: CV9202
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CureVac GmbH:

Primary Outcome Measures:
  • Number of participants with treatment related >= grade 3 adverse events (AEs). [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • overall tumor response. [ Time Frame: At Screening and every 6 weeks during study treatment until progression up to 18 months after enrollment of the last patient ] [ Designated as safety issue: No ]
  • progression free survival (PFS) and time to start of second-line treatment [ Time Frame: every 6 weeks up to 18 months after enrollment of the last patient ] [ Designated as safety issue: No ]
  • response to second-line cancer treatment [ Time Frame: every 6 weeks after completion of study treatment until progression under second-line cancer treatment or until up to 18 months after enrollment of the last patient ] [ Designated as safety issue: No ]
  • overall survival (OS) from time of first vaccination. [ Time Frame: From first study treatment until time of death assessed up to 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CV9202
CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens.
Biological: CV9202
Intradermal injection of CV9202

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.

  Eligibility

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

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
  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: NCT01915524

Contacts
Contact: Alfred Zippelius, Prof. Dr. +41 (0)61 265 ext 5074 azippelius@uhbs.ch

Locations
Austria
Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology) Recruiting
Innsbruck, Austria, 6020
Germany
HELIOS Klinikum Emil von Behring GmbH Recruiting
Berlin, Germany, 14165
Augusta-Kranken-Anstalt gGmbH Not yet recruiting
Bochum, Germany, 44791
Kliniken der Stadt Köln gGmbH Not yet recruiting
Cologne, Germany, 51109
Klinikum Esslingen GmbH Recruiting
Esslingen, Germany, 73730
University Hospital Frankfurt, Department of Medicine II: Hematology/Oncology Recruiting
Frankfurt, Germany, 60590
Thoraxklinik-Heidelberg gGmbH Not yet recruiting
Heidelberg, Germany, 69127
University Medical Center Mainz, III. Medical Clinic and Policlinic Recruiting
Mainz, Germany, 55131
Pius-Hospital Oldenburg Recruiting
Oldenburg, Germany, 26121
Switzerland
University Hospital Basel, Clinic for Oncology Recruiting
Basel, Switzerland, 4301
Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Kantonspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Kantonspital Winterthur, Oncology Recruiting
Winterthur, Switzerland, 8401
Sponsors and Collaborators
CureVac GmbH
Investigators
Principal Investigator: Alfred Zippelius, Prof. Dr. University Hospital Basel, Clinic for Medical Oncology
  More Information

Additional Information:
No publications provided

Responsible Party: CureVac GmbH
ClinicalTrials.gov Identifier: NCT01915524     History of Changes
Other Study ID Numbers: CV-9202-006
Study First Received: July 18, 2013
Last Updated: August 15, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Germany: Paul-Ehrlich-Institut
Germany: Federal Office for Radiation Protection
Switzerland: Swissmedic

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

ClinicalTrials.gov processed this record on August 26, 2014