Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)
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.
|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 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 ]
|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)|
CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens.
Intradermal injection of CV9202
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
|Contact: Alfred Zippelius, Prof. Dr.||+41 (0)61 265 ext firstname.lastname@example.org|
|Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology)||Recruiting|
|Innsbruck, Austria, 6020|
|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|
|Oldenburg, Germany, 26121|
|University Hospital Basel, Clinic for Oncology||Recruiting|
|Basel, Switzerland, 4301|
|Chur, Switzerland, 7000|
|Kantonspital St. Gallen||Recruiting|
|St. Gallen, Switzerland, 9007|
|Kantonspital Winterthur, Oncology||Recruiting|
|Winterthur, Switzerland, 8401|
|Principal Investigator:||Alfred Zippelius, Prof. Dr.||University Hospital Basel, Clinic for Medical Oncology|