Clinical trial NCT02187367: Safety & Efficacy Study of EGF Cancer Vaccine to Treat Stage IV Biomarker Positive, Wild Type EGF-R NSCLC Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Bioven Sdn. Bhd.
Sponsor class: INDUSTRY
First posted: 2014-07-11
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
6. 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.
7. Are eligible to receive first-line chemotherapy (without concurrent radiotherapy to thorax measurable lesions or consolidation radiotherapy).
8. 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.
9. 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Each patient will be followed till death occurs within study time frame of 3 years
Secondary outcomes:
measure: Safety of EGF Cancer Vaccine as assessed by Adverse Events (AEs)
timeFrame: Each patient will be followed till death occurs within study time frame of 3 years
measure: Progression-Free Survival (PFS)
timeFrame: Each patient will be followed till objective tumour progression or death (whichever occurs first) within time frame of study of 3 years
measure: Survival Rate
timeFrame: Each patient will be followed at 12 and 24 months after randomization
measure: Time to Progression (TTP)
timeFrame: Each patient will be followed till observed tumour progression within study time frame of 3 years
measure: Response Rate (RECIST criteria)
timeFrame: Each patients will be followed till death occurs within study time frame of 3 years
measure: Safety of EGF Cancer Vaccine by Laboratory Assessment
timeFrame: Each patients will be followed till death occurs within study time frame of 3 years
measure: Safety of EGF Cancer Vaccine assessed by Vital Signs
timeFrame: Each patients will be followed till death occurs within study time frame of 3 years
measure: Safety of EGF Cancer Vaccine as assessed by Physical Examination
timeFrame: Each patient will be followed till death occurs within study time frame of 3 years
measure: Quality of Life (QoL)
timeFrame: Each patient will be followed till death occurs within study time frame of 3 years
Other outcomes:
measure: Pharmacodynamics (PD) of EGF Cancer Vaccine assessed by Immune Responses
timeFrame: Each patients will be followed till death within study time frame of 3 years
measure: Efficacy assessed by KRAS and ALK rearrangements
timeFrame: At time of screening
Locations:
city: Dobrich
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment (MHAT)-Dobrich" AD
city: Sofia
country: Bulgaria
facility: MHAT for Women's Health-Nadezhda"OOD
city: Nová Ves pod Pleší
country: Czechia
facility: Nemocnice Na Pleši s.r.o. Oddelení klinické onkologie a radioterapie
city: Pardubice
country: Czechia
facility: Pardubická krajská nemocnice, a.s.c
city: Prague
country: Czechia
facility: Thomayerova nemocnice
city: Batumi
country: Georgia
facility: Cancer Center of Adjara
city: Tbilisi
country: Georgia
facility: Clinic Health House
city: Tbilisi
country: Georgia
facility: Institute of Clinical Oncology
city: Tbilisi
country: Georgia
facility: JSC, Maritime Hospital
city: Tbilisi
country: Georgia
facility: JSC, Neo Medi
city: Tbilisi
country: Georgia
facility: LTD, High Technology Medical Centre, University Clinic
city: Tbilisi
country: Georgia
facility: LTD, Medulla - Chemotherapy and Immunotherapy Clinic
city: Tbilisi
country: Georgia
facility: Research Institute Of Clinical Medicine
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale) Klinik und Poliklinik fuer Innere Medizin
state: Saale
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt Bochum
city: Hannover
country: Germany
facility: KRH Klinikum Siloah Hannover - Oststadt
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH)
city: Köln
country: Germany
facility: Kliniken der Stadt Köln GmbH
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - AöR
city: München
country: Germany
facility: LMU-München
city: Oststeinbek
country: Germany
facility: Mühlen-Apotheke
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Malacca
country: Malaysia
facility: Mahkota Medical Center
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Lahug
country: Philippines
facility: Perpetual Succour Hospital
state: Cebu City
city: Makati
country: Philippines
facility: Makati Medical Center
state: Manila
city: Pasig
country: Philippines
facility: The Medical City
state: Metro Manila
city: Quezon City
country: Philippines
facility: Lung Center of the Philippines
state: Metro Manila
city: Davao City
country: Philippines
facility: Davao Doctors hospital
city: Manila
country: Philippines
facility: Cancer Research Center
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
city: Prabuty
country: Poland
facility: Szpital Specjalistyczny w Prabutach
city: Craiova
country: Romania
facility: Centrul de Oncologie "Sf. Nectarie"
city: Otopeni
country: Romania
facility: S.C. R.T.C. Radiology Therapeutic Center S.R.L.
city: Târgu-Mureş
country: Romania
facility: SC Oncomed SRL
city: Barcelona
country: Spain
facility: Hospital Universitario Quiron Dexeus
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Mueang
country: Thailand
facility: Lopburi Cancer Hospital
state: Lopburi
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
state: Songkhla
city: Bangkok
country: Thailand
facility: Bangkok Hospital Chiang Mai
city: Lampang
country: Thailand
facility: Lampang Cancer Hospital
city: Phitsanulok
country: Thailand
facility: Buddhachinaraj Hospital
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Trust
Study officials:
affiliation: Thomayerova nemocnice, Czech Republic
name: Libor Havel, Dr.
role: PRINCIPAL_INVESTIGATOR
References: