Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)
Non-Small Cell Lung Carcinoma
Radiation: local radiation
|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|
- 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.
- 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 3 months 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 ]
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: CV9202 and local radiation
CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens.
local radiation (4x5 Gy)
Intradermal injection of CV9202Radiation: local radiation
Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01915524
|Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology)|
|Innsbruck, Austria, 6020|
|HELIOS Klinikum Emil von Behring GmbH|
|Berlin, Germany, 14165|
|Bochum, Germany, 44791|
|Kliniken der Stadt Köln gGmbH|
|Cologne, Germany, 51109|
|Klinikum Esslingen GmbH|
|Esslingen, Germany, 73730|
|University Hospital Frankfurt, Department of Medicine II: Hematology/Oncology|
|Frankfurt, Germany, 60590|
|Heidelberg, Germany, 69127|
|University Medical Center Mainz, III. Medical Clinic and Policlinic|
|Mainz, Germany, 55131|
|Oldenburg, Germany, 26121|
|University Hospital Basel, Clinic for Oncology|
|Basel, Switzerland, 4301|
|Chur, Switzerland, 7000|
|Kantonspital St. Gallen|
|St. Gallen, Switzerland, 9007|
|Kantonspital Winterthur, Oncology|
|Winterthur, Switzerland, 8401|
|Principal Investigator:||Alfred Zippelius, Prof. Dr.||University Hospital Basel, Clinic for Medical Oncology|