Clinical trial NCT01265849: Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity
Official title: Phase III Study of LI [Multikine®] Plus SOC (Surgery + Radiotherapy or Surgery + Concurrent Radiochemotherapy) in Subjects With Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate vs. SOC Only
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Oral Cavity
Squamous Cell Carcinoma of the Soft Palate
Lead sponsor: CEL-SCI Corporation
Sponsor class: INDUSTRY
Collaborators: name: Teva Branded Pharmaceutical Products R&D, Inc.
name: Orient Europharma Co., Ltd.
First posted: 2010-12-23
Enrollment: 928
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 purpose of this study was to determine whether LI administered in combination with cyclophosphamide, indomethacin and zinc in a multivitamin (CIZ) combination prior to standard of care therapy (surgery followed by radiotherapy or concurrent radiochemotherapy) is safe and will increase the overall survival of subjects with previously untreated locally advanced primary squamous cell carcinoma of the oral cavity or soft palate at a median of 3 to 5 years

Detailed description: Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US there are about 65,000 new cases annually. Ninety percent are squamous cell carcinoma of the head and neck (SCCHN). Approximately 2/3 of SCCHN patients present on their first visit with locally advanced disease. The median 3 year overall survival (OS) for these patients with existing standard of care (SOC) therapies - surgery followed by radiotherapy or concurrent radiochemotherapy - is estimated to be between 52 and 55%; the 5 year OS is approximately 43%. There are clearly many of SCCHN patients not well served by available modalities.

Regional intra or perilymphatic and/or intratumoral or peritumoral low dose cytokine therapy may have important therapeutic effects in SCCHN patients and constitute an additional anti-tumor mechanism of action different and distinct from current SOC. Leukocyte Interleukin Injection (LI) \[Multikine\] contains a defined mixture of naturally derived cytokines and chemokines with demonstrated safety and immunomodulatory activity in animals and in man in Phase I and Phase II clinical trials. LI is administered prior to SOC and in combination with low non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc (CIZ) in studies with LI. The results of these studies indicate that the local/regional injection of mixed interleukins (LI) with CIZ prior to SOC can overcome local immunosuppression, break tumor tolerance to tumor antigens and allow for a sustainable and effective anti-tumor immune response.

LI was tested in this large, global, multinational Phase III clinical trial to develop definitive proof of its efficacy and safety in treating SCCHN. The trial is an open-label randomized multi-center controlled study of LI + CIZ + SOC in subjects with advanced primary SCCHN of the oral cavity/soft palate vs. SOC \[the comparator arm\]. OS is the primary efficacy endpoint.

Eligibility criteria: Inclusion Criteria (main):

* Untreated SCCHN of oral cavity (anterior tongue, floor of mouth, cheek)/soft palate, categories T1N1-2M0,T2N1-2M0,T3N0-2M0,T4N0-2M0 (T4 allowed only if invasion of mandible is negligible i. e. 5mm or less) scheduled for SOC
* Primary tumor and any positive node(s) measurable in 2 dimensions
* Normal immune function
* No immunosuppressives with 1 year of entry
* KPS\>70/100
* Age\>18
* Male or Female (non-pregnant)
* Life expectancy \>6 months
* Able to take oral medication
* Able to provide informed consent

Exclusion Criteria (main):

* Subjects to be treated with other than SOC
* Tumor invasion of bone (also see inclusion criteria)
* Tumor classifications T1N0, T2N0, T4N3, any TN classification with M1
* Tumors in locations other than those specified in inclusion criteria
* Active peptic ulcer (or on full-dose therapeutic anti-coagulants)
* Prior resection of jugular nodes ipsilateral to tumor
* Acute or chronic viral, bacterial immune or other disease associated with abnormal immune function
* Subjects on hemodialysis or peritoneal dialysis; or having a history of
* History of asthma, allergy to fluoroquinolone antibiotics, congestive heart failure, or on hemodialysis or peritoneal dialysis
* Any condition that in the opinion of the investigator would cause the subject to be unable to participate or tolerate the protocol regimen
* Failure to meet inclusion criteria

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
measure: OS in Low Risk Subjects
timeFrame: From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary outcomes:
measure: Local Regional Control (LRC)
timeFrame: From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.
measure: LRC in Low Risk Subjects
timeFrame: From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.
measure: Progression Free Survival (PFS)
timeFrame: From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.
measure: PFS in Low Risk Subjects
timeFrame: From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.
measure: Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 2
timeFrame: Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 2
measure: Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 36
timeFrame: Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 36
measure: EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 2
timeFrame: Baseline [pre-randomization], Long Term Follow-up Month 2
measure: EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 36
timeFrame: Baseline [pre-randomization], Long Term Follow-up Month 36
measure: Statistical Comparisons of Time-to-event Outcomes (OS, LRC, PFS) Were Repeated for Varying Levels of Histopathology (HP) Markers in Low Risk Subjects
timeFrame: From the date of treatment assignment to event (LRC,PFS,OS) or the last follow-up date. Maximum follow-up was approximately 113 months.
Other outcomes:
Locations:
city: Springfield
country: United States
facility: Simmons Cancer Institute at Southern Illinois University
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System Henry Ford Hospital
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical College Of South Carolina MSC550
state: South Carolina
city: Seattle
country: United States
facility: VA Puget Sound Healthcare System & University of WA
state: Washington
city: Graz
country: Austria
facility: HNO-Klinik der medizinischen Universitat Graz
city: Lesnoy 2
country: Belarus
facility: N.N. Alexandrov Research Istitute of Oncology and Medical Radiology
state: Minsk
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Oncology Dispensary
city: Trnovac
country: Bosnia and Herzegovina
facility: University Clinical Centre Tuzla
state: Tuzla
city: Banja Luka
country: Bosnia and Herzegovina
facility: Clinical Center Banja Luka
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Hospital Mostar
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Centre University of Sarejevo Clinic for ENT
city: Hamilton
country: Canada
facility: St. Josephs Healthcare Department of Surgery
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec - L'Hotel Dieu de Quebec
city: Osijek
country: Croatia
facility: CHC Osijek
city: Slavonski Brod
country: Croatia
facility: General Hospital Dr. Josip Bencevic
city: Zagreb
country: Croatia
facility: CH Dubrava
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Zagreb Kispaticeva 12
city: Zagreb
country: Croatia
facility: KBC Sestre Milosrdnice
city: Zagreb
country: Croatia
facility: KBC Zagreb
city: Vandoeuvre les Nancy
country: France
facility: ICL 6 avenue Bourgogne CS30519
city: Debrecen
country: Hungary
facility: University of Debrecen Medical and Health Scioence Centre
state: Hajdu Bihar
city: Budapest
country: Hungary
facility: National institute of Oncology
state: Rath Gyorgy
city: Budapest
country: Hungary
facility: Semmelweis University
city: Pecs
country: Hungary
facility: University of Pecs Institute of Oncotherapy
city: Szeged
country: Hungary
facility: University of Szeged Dept of Oral and Maxillofacial Surgery
city: Szombathely
country: Hungary
facility: Markusovsky Teaching Hospital
city: Malkapet
country: India
facility: Bibi General Hospital and Cancer Centre
state: Andhra Pradesh
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences
state: Kerala
city: Amravati
country: India
facility: Sujan Regional Cancer Hospital & Amravati Cancer Foundation
state: Maharashtra
city: Aurangabad
country: India
facility: Government Medical College and Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Curie Manavata Cancer Center
state: Naka Nashik
city: Jaipur
country: India
facility: Searoc Cancer Center
state: Rajashlan
city: Coimbatore
country: India
facility: V.N. Cancer Center G. Kuppuswamy Naidu Memorial Hospital
state: Tamil Nadu
city: Madurai
country: India
facility: Meenakshi Mission Hospital and Research Centre
state: Tamil Nadu
city: Kerola
country: India
facility: Regional Cancer Center
state: Thiruvananthapuram
city: Ghaziabad
country: India
facility: Galaxy Cancer Center
state: Uttar Pradesh
city: Sha'ar Ha'Aliya
country: Israel
facility: Rambam Health Care Campus
state: Saint Haifa
city: Petaẖ Tiqwa
country: Israel
facility: Rabin Medical Center
state: Tikva
city: Naples
country: Italy
facility: National Tumor Institute of Italy
city: Taranto
country: Italy
facility: Ospedale S.G. Moscati Santissima Annunziata
city: Kuantan
country: Malaysia
facility: Dept of Head and Neck Surgery School of Medical Sciences Univ. Sains
state: Penang
city: Kuala Lumpur
country: Malaysia
facility: University Kabangsan Medical Center
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Kopernika
state: Ul Paderewskiego 4
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii
state: Ul. Artwinskiego 3
city: Warsaw
country: Poland
facility: Centrum Onkologii im. Prof. Lukaszcyka
state: Ul. Roentgena 5
city: Warszawa
country: Poland
facility: Centrum Onkologi-Instytut im. Marie Sklodowskiej-Curie
state: Ul. Roentgena 5
city: Bialystok
country: Poland
facility: ul. M. Sklodowskiej-Curie 24A
city: Krakow
country: Poland
facility: Szpital Specialistyczny im. Ludwika Rydgiera
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Klinika Otolarryngologii I Onkologii Laryngologicznej
city: Poznan
country: Poland
facility: Weilkopolskie Centrum Onkologii Klinika Chirurgii Glowy Szye Onkologii Laryngologiczne
city: Wroclaw
country: Poland
facility: Uniwersitecki Szpital Kliniczny Klinika Otolaryngologii Chirugii Glowy i Szxyi
city: Iasi
country: Romania
facility: Regional Institute of Oncology IASI
city: Targu Mures
country: Romania
facility: Spital Clinic Judetean Mures
city: Sverdlov
country: Russian Federation
facility: Sverdlovsk Regional Cancer Center
state: Ekaterinberg
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Center
state: Leningradskaya
city: Kursk
country: Russian Federation
facility: Kursk Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: Moscow
country: Russian Federation
facility: N.N. Blokhin Russian Cancer Research Center
city: Omsk
country: Russian Federation
facility: Budget Institution of Healthcare of Omsk Region Clincal Oncology Dispensary
city: Ryazan
country: Russian Federation
facility: Ryazan Clinical oncology Dispensary
city: Belgrade
country: Serbia
facility: Serbia Clinic for ENT and Maxillofacial Surgery
state: Pasterova 14
city: Belgrade
country: Serbia
facility: Clincal Center Serbia Clinic for Oral and Maxillofacial Surgery
city: Belgrade
country: Serbia
facility: Faculty of Dental Medicine Clinic for Maxillofacial Surgery
city: Belgrade
country: Serbia
facility: Military Medical Academy Clinic for Maxillofacial Surgery
city: Nis
country: Serbia
facility: Clinical Center Nis center for Oncology
city: Nis
country: Serbia
facility: Clinic for Stomatology department for maxillofacial Surgery
city: Novi Sad
country: Serbia
facility: Clinical center Vojvodina Clinic for ORL
city: Novi Sad
country: Serbia
facility: Clinical Centre Vojvodina Clinic for Maxillofacial Surgery
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario de Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Madrid North Universitaro de Sanchinnaro
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Univ. de Santiago
city: Valencia
country: Spain
facility: Consorsio Hospital General Universitario de valencia
city: Colombo
country: Sri Lanka
facility: National Cancer Institute Dept of Clinical Oncology & Radiotherapy
city: Galle
country: Sri Lanka
facility: Oncology Unit Teaching Hospital Karapitya
city: Niaosong
country: Taiwan
facility: Kaohsiung Branch Chang Gung Memorial Hospital
state: Kaohsiung
city: Taipei
country: Taiwan
facility: National Cheng Kung University Hospital
state: Tainan
city: Chengshan
country: Taiwan
facility: National Taiwan Research Hospital
state: Taipei
city: Guishan
country: Taiwan
facility: Linkou Branch Chang Gung Memorial Hospital
state: Taoyuan
city: Chang-hua
country: Taiwan
facility: Changua Christian Hospital
city: Hualien City
country: Taiwan
facility: Buddhist Tzu Chi General Hospital, Hualien Branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Shin-Kong Wu Ho-Su Memorial Hospital
city: Nai- Muang
country: Thailand
facility: Khon Kaen University Dept of Otolaryngology
city: Ankara
country: Turkey
facility: Haceteppe University Dept of Otolaryngology - Head and Neck Surgery
city: Istanbul
country: Turkey
facility: Acibadem University Maslak Hospital ENT Department
city: Cherkasy
country: Ukraine
facility: Cherkasky Regional Oncological Dyspensary Dept. Head and Neck tumour
city: Dnepropetrovsk
country: Ukraine
facility: Clinical Diagnostic Laboratory of Dnepropetrovsk Municipal Institution City Multidisciplinary Clinical Hospital No. 4
city: Donetsk
country: Ukraine
facility: Donetsk Regional Antitumor Center
city: Kharkiv
country: Ukraine
facility: Grigoriev Institute for Medical Radiology of National Academy of Medical Science of Ukraine Dept. of Remote, Combined Radiation and Complex Therapy
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center Dept. Of Head and Neck Tumour
city: Kiev
country: Ukraine
facility: Kiev City Clinical Oncology Center of the Main Health Care Dept of Kiev Day Hospital Radiotherapy Dept.
city: Kiev
country: Ukraine
facility: Kiev City Clinical Oncology Center of the Main Health Care Dept. of the Kiev Day Hospital
city: Lviv
country: Ukraine
facility: Lviv State OncologyRegional treatment and Diagnostic Center
city: Sumy
country: Ukraine
facility: Sumy Regional Clinical Oncology Dyspensary
city: Zaporiz'ka Oblast'
country: Ukraine
facility: Zaporiz'ka Regional Clinical Oncology Dispensary
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
Study officials:
affiliation: CEL-SCI Corporation
name: Eyal Talor, PhD
role: STUDY_DIRECTOR
References: