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

NCT01915524 | Terminated Phase 1 DMC

• 1 other identifier: CV-9202-006
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 13

Brief 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 with an EGFR tyrosine kinase inhibitor.

Conditions

Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (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.

  up to 40 months

Secondary Outcomes (6)

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

  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.

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

• overall tumor response.

  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

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

• response to second-line cancer treatment

  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

Study Arms (1)

CV9202 and local radiation

EXPERIMENTAL

CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens. local radiation (4x5 Gy)

Biological: CV9202; Radiation: local radiation

Interventions

CV9202 BIOLOGICAL

Intradermal injection of CV9202

CV9202 and local radiation

local radiation RADIATION

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

CV9202 and local radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• CureVac: lead

Study Sites (13)

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

Innsbruck, 6020, Austria

Location

HELIOS Klinikum Emil von Behring GmbH

Berlin, 14165, Germany

Location

Augusta-Kranken-Anstalt gGmbH

Bochum, 44791, Germany

Location

Kliniken der Stadt Köln gGmbH

Cologne, 51109, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

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

Frankfurt, 60590, Germany

Location

Thoraxklinik-Heidelberg gGmbH

Heidelberg, 69127, Germany

Location

University Medical Center Mainz, III. Medical Clinic and Policlinic

Mainz, 55131, Germany

Location

Pius-Hospital Oldenburg

Oldenburg, 26121, Germany

Location

University Hospital Basel, Clinic for Oncology

Basel, 4301, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Kantonspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonspital Winterthur, Oncology

Winterthur, 8401, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 30736848 DERIVED

• 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.

  PMID: 25288198 DERIVED

Related Links

• Click here for more information about CureVac

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alfred Zippelius, Prof. Dr.

  University Hospital Basel, Clinic for Medical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2013
• First Posted: August 5, 2013
• Study Start: April 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 5, 2016

Record last verified: 2016-08

Locations

DE (8); AU (1); CH (4)