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Non-Small Cell Lung CarcinomaPhase 1NCT01915524

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

A Phase 1 study testing CV9202 and local radiation in people with Non-Small Cell Lung Carcinoma, run by CureVac at 13 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Carcinoma
What is being tested?
CV9202 and local radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
13 sitesin 3 countries
Study dates
Apr 2013to Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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)
Show all 16Show fewer
  • 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
  • For patients in stratum 1, maintenance therapy with pemetrexed should be indicated as to the investigator's opinion
  • 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)
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 1

Who cannot join

  • Previous active immunotherapy for NSCLC (including vaccination, therapy with anti-CTLA4 antibodies)
  • Estimated life expectancy ≤ 3 months
  • Need for immunosuppressive treatment including daily systemic steroid doses of ≥ 10 mg prednisone equivalent per day
  • 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
  • Concurrent or planned major surgery
  • Prior splenectomy or prior allogeneic bone marrow transplantation
Show all 18Show fewer
  • History of pneumonitis
  • Documented history or active autoimmune disorders with the exception of vitiligo, diabetes mellitus type 1 or autoimmune thyroiditis requiring hormone replacement only
  • Primary or secondary immune deficiency
  • Allergies to any components of the study drug including allergy to protamine hydrochloride (e.g. allergy to protamine-containing insulin) or fish allergy
  • Seropositive for HIV, HBV, HCV or any other infection requiring anti-infection therapy
  • For patients in stratum 3: persisting >= grade 3 skin rash at time of enrollment
  • 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
  • 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
  • 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)
  • History of encephalitis or multiple sclerosis
  • Active inflammatory conditions such as inflammatory bowel disease

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

Germany8 sites

  • HELIOS Klinikum Emil von Behring GmbH

    Berlin, 14165

  • Augusta-Kranken-Anstalt gGmbH

    Bochum, 44791

  • Kliniken der Stadt Köln gGmbH

    Cologne, 51109

  • Klinikum Esslingen GmbH

    Esslingen am Neckar, 73730

  • University Hospital Frankfurt, Department of Medicine II: Hematology/Oncology

    Frankfurt, 60590

  • Thoraxklinik-Heidelberg gGmbH

    Heidelberg, 69127

  • University Medical Center Mainz, III. Medical Clinic and Policlinic

    Mainz, 55131

  • Pius-Hospital Oldenburg

    Oldenburg, 26121

Other trials in Germany

Switzerland4 sites

  • University Hospital Basel, Clinic for Oncology

    Basel, 4301

  • Kantonsspital Graubünden

    Chur, 7000

  • Kantonspital St. Gallen

    Sankt Gallen, 9007

  • Kantonspital Winterthur, Oncology

    Winterthur, 8401

Other trials in Switzerland

Austria1 site

  • Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology)

    Innsbruck, 6020

Other trials in Austria

About this study

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

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.

Read the 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.

Being tested
CV9202, local radiation
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CV9202Biological

    Intradermal injection of CV9202

  • local radiationRadiation

    Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week

Study groups in NCT01915524
Study groupRoleWhat they receive
CV9202 and local radiationExperimentalCV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens. local radiation (4x5 Gy)
Receives: Biological: CV9202; Radiation: local radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with treatment related >= grade 3 adverse events (AEs).

    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.

    Measured: up to 40 months

Secondary outcomes (6)

  1. humoral and cellular immune responses against the 6 antigens encoded by CV9202.

    Measured: assessments at baseline, Day 19, Day 61 after start of study treatment

  2. 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.

    Measured: Assessment at baseline, Day 19, Day 61 and 12 weeks, 24 weeks and 48 weeks after Day 57

  3. overall tumor response.

    Measured: At Screening and every 6 weeks during study treatment until progression up to 18 months after start of treatment of the last patient enrolled

  4. progression free survival (PFS) and time to start of second-line treatment

    Measured: every 6 weeks up to 18 months after start of treatment of the last patient enrolled

  5. response to second-line cancer treatment

    Measured: 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

  6. overall survival (OS) from time of first vaccination.

    Measured: From first study treatment until time of death assessed up to 40 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2013 (estimated)
  2. Study startApr 2013
  3. Primary completionJul 2016
  4. Study completionJul 2016

Why it stopped: Slow recruitment in stratum 3: enrolled only 2 instead of 8 pts. within predicted time

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01915524
Sponsor's protocol ID
CV-9202-006
Status last verified
Aug 2016
First submitted
18 Jul 2013
Last updated
5 Aug 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Papachristofilou A, Hipp MM, Klinkhardt U, Fruh M, Sebastian M, Weiss C, Pless M, Cathomas R, Hilbe W, Pall G, Wehler T, Alt J, Bischoff H, Geissler M, Griesinger F, Kallen KJ, Fotin-Mleczek M, Schroder A, Scheel B, Muth A, Seibel T, Stosnach C, Doener F, Hong HS, Koch SD, Gnad-Vogt U, Zippelius A. Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. J Immunother Cancer. 2019 Feb 8;7(1):38. doi: 10.1186/s40425-019-0520-5.

    PubMed 30736848

  • Sebastian M, Papachristofilou A, Weiss C, Fruh M, Cathomas R, Hilbe W, Wehler T, Rippin G, Koch SD, Scheel B, Fotin-Mleczek M, Heidenreich R, Kallen KJ, Gnad-Vogt U, Zippelius A. Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive(R)) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer. BMC Cancer. 2014 Oct 6;14:748. doi: 10.1186/1471-2407-14-748.

    PubMed 25288198

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CV9202 and local radiation in people with Non-Small Cell Lung Carcinoma, run by CureVac at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Germany, Switzerland, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow recruitment in stratum 3: enrolled only 2 instead of 8 pts. within predicted time). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment related >= grade 3 adverse events (AEs). (time frame: up to 40 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01915524, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2016.

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