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
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Carcinoma||Biological: CV9202 Radiation: local radiation||Phase 1|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||July 2016|
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 CV9202
Radiation: local radiation
Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week
- 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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|