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

NCT02187367 | Terminated Phase 3 DMC

• 2 other identifiers: BV-NSCLC-0022013-005335-25
• Study Type: interventional
• Target: 106
• Locations: 11 countries
• Sites: 51

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

• 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

• Survival Rate

  Each patient will be followed at 12 and 24 months after randomization

• Time to Progression (TTP)

  Each patient will be followed till observed tumour progression within study time frame of 3 years

• Response Rate (RECIST criteria)

  Each patients will be followed till death occurs within study time frame of 3 years

Other Outcomes (2)

• Pharmacodynamics (PD) of EGF Cancer Vaccine assessed by Immune Responses

  Each patients will be followed till death within study time frame of 3 years

• Efficacy assessed by KRAS and ALK rearrangements

  At time of screening

Study Arms (2)

EGF Vaccine

EXPERIMENTAL

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

Biological: EGF Vaccine

Best Supportive Care

NO INTERVENTION

Patients in this arm will receive best supportive care

Interventions

EGF Vaccine BIOLOGICAL

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.

Also known as: Cyclophosphamide and the recombinant human rEGF-P64K/Montanide ISA 51

EGF Vaccine

Eligibility Criteria

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

You may qualify if:

• Are aged 18 or older.
• Have serum EGF concentration \>250 pg/ml determined from sample taken at screening.
• Have wild type EGF-R sequence.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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
• 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.
• Are eligible to receive first-line chemotherapy (without concurrent radiotherapy to thorax measurable lesions or consolidation radiotherapy).
• 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.
• 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.

You may not qualify if:

• Patient has no measurable disease (as defined by RECIST Criteria, version 1.1).
• Patient has EGF-R mutation.
• Patient has EGF serum concentration below required threshold.
• Patient is a candidate for concurrent chemo-radiotherapy or post chemo thoracic radiotherapy.
• Patient has a history of known or suspected central nervous system (CNS) metastases.
• 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.
• Patient is taking immunosuppressant drugs such as azathioprine, tacrolimus, cyclosporine, etc. Use is not permitted within 1 month before Screening.
• Patient is taking any other immunotherapy.
• Patient has primary or secondary immunodeficiencies (e.g. documented Human Immunodeficiency Virus \[HIV\]).
• Patient has autoimmune disease.
• Patient has undergone splenectomy.
• 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.
• Patient has neurotoxicity (Grade ≥2).
• Patient has diarrhoea (Grade ≥2).
• Patient has received other vaccines (with the exception of the influenza vaccine), within 1 month before Screening.

Sponsors & Collaborators

• Bioven Europe: lead

Study Sites (51)

"Multiprofile Hospital for Active Treatment (MHAT)-Dobrich" AD

Dobrich, Bulgaria

Location

MHAT for Women's Health-Nadezhda"OOD

Sofia, Bulgaria

Location

Nemocnice Na Pleši s.r.o. Oddelení klinické onkologie a radioterapie

Nová Ves pod Pleší, Czechia

Location

Pardubická krajská nemocnice, a.s.c

Pardubice, Czechia

Location

Thomayerova nemocnice

Prague, Czechia

Location

Cancer Center of Adjara

Batumi, Georgia

Location

Clinic Health House

Tbilisi, Georgia

Location

Institute of Clinical Oncology

Tbilisi, Georgia

Location

JSC, Maritime Hospital

Tbilisi, Georgia

Location

JSC, Neo Medi

Tbilisi, Georgia

Location

LTD, High Technology Medical Centre, University Clinic

Tbilisi, Georgia

Location

LTD, Medulla - Chemotherapy and Immunotherapy Clinic

Tbilisi, Georgia

Location

Research Institute Of Clinical Medicine

Tbilisi, Georgia

Location

Universitätsklinikum Halle (Saale) Klinik und Poliklinik fuer Innere Medizin

Halle, Saale, Germany

Location

Augusta-Kranken-Anstalt Bochum

Bochum, Germany

Location

Kliniken der Stadt Köln GmbH

Cologne, Germany

Location

KRH Klinikum Siloah Hannover - Oststadt

Hanover, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, Germany

Location

Universitätsklinikum Leipzig - AöR

Leipzig, Germany

Location

LMU-München

München, Germany

Location

Mühlen-Apotheke

Oststeinbek, Germany

Location

Hospital Sultanah Bahiyah

Alor Star, Kedah, Malaysia

Location

Sarawak General Hospital

Kuching, Malaysia

Location

Mahkota Medical Center

Malacca, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, Malaysia

Location

Perpetual Succour Hospital

Lahug, Cebu City, Philippines

Location

Makati Medical Center

Makati, Manila, Philippines

Location

The Medical City

Pasig, National Capital Region, Philippines

Location

Lung Center of the Philippines

Quezon City, National Capital Region, Philippines

Location

Davao Doctors hospital

Davao City, Philippines

Location

Cancer Research Center

Manila, Philippines

Location

Philippine General Hospital

Manila, Philippines

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, Poland

Location

Szpital Specjalistyczny w Prabutach

Prabuty, Poland

Location

Centrul de Oncologie "Sf. Nectarie"

Craiova, Romania

Location

S.C. R.T.C. Radiology Therapeutic Center S.R.L.

Otopeni, Romania

Location

SC Oncomed SRL

Târgu Mureş, Romania

Location

Hospital Universitario Quiron Dexeus

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario Fundación Jimenez Díaz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Spain

Location

Lopburi Cancer Hospital

Mueang, Changwat Lop Buri, Thailand

Location

Songklanagarind Hospital

Hat Yai, Changwat Songkhla, Thailand

Location

Bangkok Hospital Chiang Mai

Bangkok, Thailand

Location

Lampang Cancer Hospital

Lampang, Thailand

Location

Buddhachinaraj Hospital

Phitsanulok, Thailand

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

University Hospital Southampton NHS Trust

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Libor Havel, Dr.

  Thomayerova nemocnice, Czech Republic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 11, 2014
• Study Start: May 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: September 6, 2019
• Last Updated: September 10, 2019

Record last verified: 2019-09

Locations

GE (8); RO (3); PL (2); MY (4); BU (2); ES (5); CZ (3); DE (9); TH (5); PH (7); GB (3)