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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— EGF  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02187367
• Other study ID #: BV-NSCLC-002
• Secondary ID: 2013-005335-25
• Status: Terminated
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: September 6, 2019

Study information

• Verified date: September 2019
• Source: Bioven Sdn. Bhd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 106
• Est. completion date: September 6, 2019
• Est. primary completion date: May 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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.

Locations

Country	Name	City	State
Bulgaria	"Multiprofile Hospital for Active Treatment (MHAT)-Dobrich" AD	Dobrich
Bulgaria	MHAT for Women's Health-Nadezhda"OOD	Sofia
Czechia	Nemocnice Na Pleši s.r.o. Oddelení klinické onkologie a radioterapie	Nová Ves pod Pleší
Czechia	Pardubická krajská nemocnice, a.s.c	Pardubice
Czechia	Thomayerova nemocnice	Prague
Georgia	Cancer Center of Adjara	Batumi
Georgia	Clinic Health House	Tbilisi
Georgia	Institute of Clinical Oncology	Tbilisi
Georgia	JSC, Maritime Hospital	Tbilisi
Georgia	JSC, Neo Medi	Tbilisi
Georgia	LTD, High Technology Medical Centre, University Clinic	Tbilisi
Georgia	LTD, Medulla - Chemotherapy and Immunotherapy Clinic	Tbilisi
Georgia	Research Institute Of Clinical Medicine	Tbilisi
Germany	Augusta-Kranken-Anstalt Bochum	Bochum
Germany	Universitätsklinikum Halle (Saale) Klinik und Poliklinik fuer Innere Medizin	Halle	Saale
Germany	KRH Klinikum Siloah Hannover - Oststadt	Hannover
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel
Germany	Kliniken der Stadt Köln GmbH	Köln
Germany	Universitätsklinikum Leipzig - AöR	Leipzig
Germany	LMU-München	München
Germany	Mühlen-Apotheke	Oststeinbek
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Sarawak General Hospital	Kuching
Malaysia	Mahkota Medical Center	Malacca
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Philippines	Davao Doctors hospital	Davao City
Philippines	Perpetual Succour Hospital	Lahug	Cebu City
Philippines	Makati Medical Center	Makati	Manila
Philippines	Cancer Research Center	Manila
Philippines	Philippine General Hospital	Manila
Philippines	The Medical City	Pasig	Metro Manila
Philippines	Lung Center of the Philippines	Quezon City	Metro Manila
Poland	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc	Olsztyn
Poland	Szpital Specjalistyczny w Prabutach	Prabuty
Romania	Centrul de Oncologie "Sf. Nectarie"	Craiova
Romania	S.C. R.T.C. Radiology Therapeutic Center S.R.L.	Otopeni
Romania	SC Oncomed SRL	Târgu-Mures
Spain	Hospital Universitario Quiron Dexeus	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Fundación Jimenez Díaz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Thailand	Bangkok Hospital Chiang Mai	Bangkok
Thailand	Songklanagarind Hospital	Hat Yai	Songkhla
Thailand	Lampang Cancer Hospital	Lampang
Thailand	Lopburi Cancer Hospital	Mueang	Lopburi
Thailand	Buddhachinaraj Hospital	Phitsanulok
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	University Hospital Southampton NHS Trust	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Bioven Europe

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Georgia,  Germany,  Malaysia,  Philippines,  Poland,  Romania,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamics (PD) of EGF Cancer Vaccine assessed by Immune Responses	To assess the serum EGF concentration and anti-EGF antibody titers with response before and after to the study treatment	Each patients will be followed till death within study time frame of 3 years
Other	Efficacy assessed by KRAS and ALK rearrangements	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	At time of screening
Primary	Overall Survival (OS)	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.	Each patient will be followed till death occurs within study time frame of 3 years
Secondary	Safety of EGF Cancer Vaccine as assessed by Adverse Events (AEs)	To assess the frequency and number of patients develop AEs, related AEs, serious AEs (SAEs) and AEs leading to withdrawal or death	Each patient will be followed till death occurs within study time frame of 3 years
Secondary	Progression-Free Survival (PFS)	Progression parameters include radiological or clinical progression, withdrawal due to progression, and death due to any cause.	Each patient will be followed till objective tumour progression or death (whichever occurs first) within time frame of study of 3 years
Secondary	Survival Rate	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.	Each patient will be followed at 12 and 24 months after randomization
Secondary	Time to Progression (TTP)	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.	Each patient will be followed till observed tumour progression within study time frame of 3 years
Secondary	Response Rate (RECIST criteria)	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.	Each patients will be followed till death occurs within study time frame of 3 years
Secondary	Safety of EGF Cancer Vaccine by Laboratory Assessment	To assess haematology, biochemistry and urinalysis parameters	Each patients will be followed till death occurs within study time frame of 3 years
Secondary	Safety of EGF Cancer Vaccine assessed by Vital Signs	To assess systolic and diastolic blood pressure, body temperature and pulse rate	Each patients will be followed till death occurs within study time frame of 3 years
Secondary	Safety of EGF Cancer Vaccine as assessed by Physical Examination	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	Each patient will be followed till death occurs within study time frame of 3 years
Secondary	Quality of Life (QoL)	To assess the general physical health of patients with a 36-item, short-form health survey until disease progression	Each patient will be followed till death occurs within study time frame of 3 years