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Safety & Efficacy Study of EGF Cancer Vaccine to Treat Stage IV Biomarker Positive, Wild Type EGF-R NSCLC Patients

Sponsor
Bioven Europe (Industry)
Overall Status
Terminated
CT.gov ID
NCT02187367
Collaborator
(none)
106
Enrollment
51
Locations
2
Arms
52.2
Actual Duration (Months)
2.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The vaccine contains humanized recombinant antigen (EGF - Epithelial Growth Factor) and an adjuvant. The antibodies induced by vaccination will react with circulating EGF leading to removal of EGF from the circulation. As a result, binding to its target EGF-Receptor is prevented. Blocking of EGF-Receptor is preventing activation and stimulation of proliferation of tumour cell. A Phase 3 clinical trial on the EGF vaccine is ongoing in Cuba. The result from previous studies demonstrated positive correlation between extended survival and immune response against the vaccination in the late-stage NSCLC patients' age below 60 with improved quality of life. The purpose of this international Phase 3 trial is to determine whether the recombinant human EGF cancer vaccine is safe, immunogenic and effective in the treatment of stage IV NSCLC patients who are positive in the selective EGF biomarker and wild type EGF-Receptor compared to standard treatment and supportive care.

Condition or Disease Intervention/Treatment Phase
  • Biological: EGF Vaccine
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
106 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 3 Open-label, Multicentre, Randomised Trial to Establish Safety & Efficacy of an EGF Cancer Vaccine in Inoperable, Stage IV Biomarker Positive,Wild Type EGF-R NSCLC Patients Eligible to Receive Standard Treatment and Supportive Care
Actual Study Start Date :
May 1, 2015
Actual Primary Completion Date :
May 1, 2019
Actual Study Completion Date :
Sep 6, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: EGF Vaccine

Patients in this arm will receive a low dose of cyclophosphamide and the recombinant human rEGF-P64K/Montanide ISA 51

Biological: EGF Vaccine
1.2mL of conjugate-adjuvant mix injection at four sites during the Post First-Line Chemotherapy. Reduced dose of injection at two sites during the Pre-Progression Phase.
Other Names:
  • Cyclophosphamide and the recombinant human rEGF-P64K/Montanide ISA 51

    		•
    No Intervention: Best Supportive Care

    Patients in this arm will receive best supportive care

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Each patient will be followed till death occurs within study time frame of 3 years]

      To assess overall survival (OS) of an EGF cancer vaccine in inoperable, stage IV biomarker positive, wild type EGF-R, NSCLC patients compared to the control group receiving best treatment and supportive care. OS is defined as the time from randomisation to death due to any cause.

    Secondary Outcome Measures

    1. Safety of EGF Cancer Vaccine as assessed by Adverse Events (AEs) [Each patient will be followed till death occurs within study time frame of 3 years]

      To assess the frequency and number of patients develop AEs, related AEs, serious AEs (SAEs) and AEs leading to withdrawal or death

    2. Progression-Free Survival (PFS) [Each patient will be followed till objective tumour progression or death (whichever occurs first) within time frame of study of 3 years]

      Progression parameters include radiological or clinical progression, withdrawal due to progression, and death due to any cause.

    3. Survival Rate [Each patient will be followed at 12 and 24 months after randomization]

      To assess the percentage of patients that are alive at 12 months and 24 months in EGF cancer vaccine study group compared to control group.

    4. Time to Progression (TTP) [Each patient will be followed till observed tumour progression within study time frame of 3 years]

      To assess Time to Progression (TTP) from the time of randomisation to first documented disease progression of EGF cancer vaccine study group patients compared to control group.

    5. Response Rate (RECIST criteria) [Each patients will be followed till death occurs within study time frame of 3 years]

      To assess the percentage of patients with a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria Version 1.1.

    6. Safety of EGF Cancer Vaccine by Laboratory Assessment [Each patients will be followed till death occurs within study time frame of 3 years]

      To assess haematology, biochemistry and urinalysis parameters

    7. Safety of EGF Cancer Vaccine assessed by Vital Signs [Each patients will be followed till death occurs within study time frame of 3 years]

      To assess systolic and diastolic blood pressure, body temperature and pulse rate

    8. Safety of EGF Cancer Vaccine as assessed by Physical Examination [Each patient will be followed till death occurs within study time frame of 3 years]

      To assess eyes, neurological and cardiovascular systems, lungs, abdomen, and any other areas with signs and symptoms of disease, and of the head, neck, ears, nose, mouth, throat, thyroid, lymph nodes and extremities

    9. Quality of Life (QoL) [Each patient will be followed till death occurs within study time frame of 3 years]

      To assess the general physical health of patients with a 36-item, short-form health survey until disease progression

    Other Outcome Measures

    1. Pharmacodynamics (PD) of EGF Cancer Vaccine assessed by Immune Responses [Each patients will be followed till death within study time frame of 3 years]

      To assess the serum EGF concentration and anti-EGF antibody titers with response before and after to the study treatment

    2. Efficacy assessed by KRAS and ALK rearrangements [At time of screening]

      For the analysis of oncogenes Kirsten rat sarcoma (KRAS) and anaplastic lymphoma kinase (ALK), a formalin-fixed, paraffin embedded (FFPE) sample of the biopsy tumour tissue, ideally taken from biopsy obtained at disease diagnosis will be prepared and shipped for central analysis

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Are aged 18 or older.

    2. Have serum EGF concentration >250 pg/ml determined from sample taken at screening.

    3. Have wild type EGF-R sequence.

    4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    5. Have adequate bone marrow, liver and renal function, as assessed by the Investigator.

    A sample taken at Screening should confirm that:

    • White blood cell (WBC) count ≥ 3000 per µL

    • Platelet count ≥ 100,000 per µL

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN when liver metastases are present)

    • Total bilirubin ≤ 1.5 x ULN

    • Serum creatinine ≤ 1.5 x ULN

    1. Have histologically and/or cytologically confirmed diagnosis of NSCLC, corresponding to locally and regionally advanced inoperable disease (Stage IV [as defined by the American Joint Committee on Cancer staging system- TNM 7th edition 2010]) excluding brain metastases.

    2. Are eligible to receive first-line chemotherapy (without concurrent radiotherapy to thorax measurable lesions or consolidation radiotherapy).

    3. Agree to use double-barrier contraception (males and females alike [if applicable]). A negative pregnancy test must be documented at Screening for females of childbearing potential.

    Note: Females of childbearing potential are defined as those women with less than 2 years after last menstruation and not surgically sterile, while post-menopausal refers to those women with at least 2 years from last menstruation.

    1. Have signed a voluntary written informed consent form (ICF). Patients should be cooperative, willing and able to participate and adhere to the Protocol requirements, including their availability for the follow-up.
    Exclusion Criteria:

    1. Patient has no measurable disease (as defined by RECIST Criteria, version 1.1).

    2. Patient has EGF-R mutation.

    3. Patient has EGF serum concentration below required threshold.

    4. Patient is a candidate for concurrent chemo-radiotherapy or post chemo thoracic radiotherapy.

    5. Patient has a history of known or suspected central nervous system (CNS) metastases.

    6. Patient has a history of primary malignancy (except resected non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix), unless in complete remission and off all chemotherapy and/or radiotherapy for that disease for a minimum of 5 years. Any palliative radiotherapy to alleviate pain in bone metastases is permitted.

    7. Patient is taking immunosuppressant drugs such as azathioprine, tacrolimus, cyclosporine, etc. Use is not permitted within 1 month before Screening.

    8. Patient is taking any other immunotherapy.

    9. Patient has primary or secondary immunodeficiencies (e.g. documented Human Immunodeficiency Virus [HIV]).

    10. Patient has autoimmune disease.

    11. Patient has undergone splenectomy.

    12. Patient is taking oral, intramuscular or intravenous corticosteroids. Use is not permitted within 1 month before Screening. Inhaled corticosteroids to treat respiratory insufficiency (e.g. chronic obstructive pulmonary disease [COPD]), or topical steroids are permitted.

    13. Patient has neurotoxicity (Grade ≥2).

    14. Patient has diarrhoea (Grade ≥2).

    15. Patient has received other vaccines (with the exception of the influenza vaccine), within 1 month before Screening.

    16. Patient has a history of any severe or life-threatening hypersensitivity reaction.

    17. Patient has an unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal and metabolic disease).

    18. Patient has recent history (within 6 months before Screening) of chronic alcohol or drug abuse which may compromise the patient's safety or ability to participate in study activities.

    19. Patient has a history of psychiatric disorder that prevents patients from providing informed consent or following Protocol instructions.

    20. Patient is currently enrolled in an investigational device or drug trial, or <1 month since completing an investigational device or drug trial.

    21. Female patients who are pregnant or lactating.

    22. Patient has any other factor that in the opinion of the Investigator (or designee) would make the patient unsafe or unsuitable for the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 "Multiprofile Hospital for Active Treatment (MHAT)-Dobrich" AD Dobrich Bulgaria
    2 MHAT for Women's Health-Nadezhda"OOD Sofia Bulgaria
    3 Nemocnice Na Pleši s.r.o. Oddelení klinické onkologie a radioterapie Nová Ves pod Pleší Czechia
    4 Pardubická krajská nemocnice, a.s.c Pardubice Czechia
    5 Thomayerova nemocnice Prague Czechia
    6 Cancer Center of Adjara Batumi Georgia
    7 Clinic Health House Tbilisi Georgia
    8 Institute of Clinical Oncology Tbilisi Georgia
    9 JSC, Maritime Hospital Tbilisi Georgia
    10 JSC, Neo Medi Tbilisi Georgia
    11 LTD, High Technology Medical Centre, University Clinic Tbilisi Georgia
    12 LTD, Medulla - Chemotherapy and Immunotherapy Clinic Tbilisi Georgia
    13 Research Institute Of Clinical Medicine Tbilisi Georgia
    14 Universitätsklinikum Halle (Saale) Klinik und Poliklinik fuer Innere Medizin Halle Saale Germany
    15 Augusta-Kranken-Anstalt Bochum Bochum Germany
    16 KRH Klinikum Siloah Hannover - Oststadt Hannover Germany
    17 Thoraxklinik Heidelberg gGmbH Heidelberg Germany
    18 Universitätsklinikum Schleswig-Holstein (UKSH) Kiel Germany
    19 Kliniken der Stadt Köln GmbH Köln Germany
    20 Universitätsklinikum Leipzig - AöR Leipzig Germany
    21 LMU-München München Germany
    22 Mühlen-Apotheke Oststeinbek Germany
    23 Hospital Sultanah Bahiyah Alor Setar Kedah Malaysia
    24 Sarawak General Hospital Kuching Malaysia
    25 Mahkota Medical Center Malacca Malaysia
    26 Hospital Pulau Pinang Pulau Pinang Malaysia
    27 Perpetual Succour Hospital Lahug Cebu City Philippines
    28 Makati Medical Center Makati Manila Philippines
    29 The Medical City Pasig Metro Manila Philippines
    30 Lung Center of the Philippines Quezon City Metro Manila Philippines
    31 Davao Doctors hospital Davao City Philippines
    32 Cancer Research Center Manila Philippines
    33 Philippine General Hospital Manila Philippines
    34 Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc Olsztyn Poland
    35 Szpital Specjalistyczny w Prabutach Prabuty Poland
    36 Centrul de Oncologie "Sf. Nectarie" Craiova Romania
    37 S.C. R.T.C. Radiology Therapeutic Center S.R.L. Otopeni Romania
    38 SC Oncomed SRL Târgu-Mureş Romania
    39 Hospital Universitario Quiron Dexeus Barcelona Spain
    40 Hospital General Universitario Gregorio Marañón Madrid Spain
    41 Hospital Universitario Fundación Jimenez Díaz Madrid Spain
    42 Hospital Universitario Puerta de Hierro Madrid Spain
    43 Hospital Regional Universitario de Málaga Málaga Spain
    44 Lopburi Cancer Hospital Mueang Lopburi Thailand
    45 Songklanagarind Hospital Hat Yai Songkhla Thailand
    46 Bangkok Hospital Chiang Mai Bangkok Thailand
    47 Lampang Cancer Hospital Lampang Thailand
    48 Buddhachinaraj Hospital Phitsanulok Thailand
    49 Aberdeen Royal Infirmary Aberdeen United Kingdom
    50 Nottingham University Hospitals Nottingham United Kingdom
    51 University Hospital Southampton NHS Trust Southampton United Kingdom

    Sponsors and Collaborators

    • Bioven Europe

    Investigators

    • Principal Investigator: Libor Havel, Dr., Thomayerova nemocnice, Czech Republic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bioven Europe
    ClinicalTrials.gov Identifier:
    NCT02187367
    Other Study ID Numbers:
    • BV-NSCLC-002
    • 2013-005335-25
    First Posted:
    Jul 11, 2014
    Last Update Posted:
    Sep 10, 2019
    Last Verified:
    Sep 1, 2019
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Cyclophosphamide

    Study Results

    No Results Posted as of Sep 10, 2019