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

August 4, 2016 updated by: CureVac

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology)
  • Germany
      • Berlin, Germany, 14165
        • Helios Klinikum Emil von Behring GmbH
      • Bochum, Germany, 44791
        • Augusta-Kranken-Anstalt gGmbH
      • Cologne, Germany, 51109
        • Kliniken der Stadt Koln gGmbH
      • Esslingen, Germany, 73730
        • Klinikum Esslingen GmbH
      • Frankfurt, Germany, 60590
        • University Hospital Frankfurt, Department of Medicine II: Hematology/Oncology
      • Heidelberg, Germany, 69127
        • Thoraxklinik-Heidelberg gGmbH
      • Mainz, Germany, 55131
        • University Medical Center Mainz, III. Medical Clinic and Policlinic
      • Oldenburg, Germany, 26121
        • Pius-Hospital Oldenburg
  • Switzerland
      • Basel, Switzerland, 4301
        • University Hospital Basel, Clinic for Oncology
      • Chur, Switzerland, 7000
        • Kantonsspital Graubünden
      • St. Gallen, Switzerland, 9007
        • Kantonspital St. Gallen
      • Winterthur, Switzerland, 8401
        • Kantonspital Winterthur, Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CV9202 and local radiation

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

local radiation (4x5 Gy)
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
up to 40 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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
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
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
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
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
From first study treatment until time of death assessed up to 40 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CureVac

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alfred Zippelius, Prof. Dr., University Hospital Basel, Clinic for Medical Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 5, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CV-9202-006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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