Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity

Squamous Cell Carcinoma of the Oral Cavity Clinical Trial

— IT-MATTERS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01265849
• Other study ID #: CS001P3
• Secondary ID: 2010-019952-35
• Status: Completed
• Phase: Phase 3
• Start date: December 2010
• Est. completion date: December 4, 2020

Study information

• Verified date: August 2022
• Source: CEL-SCI Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 928
• Est. completion date: December 4, 2020
• Est. primary completion date: May 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Oral Cavity
• Squamous Cell Carcinoma of the Soft Palate

Intervention

Biological:
• LI
LI 400 IU (2.0mL total daily) 1.0 mL peritumoral, 1.0 mL perilymphatic 5x weekly x3 consecutive weeks administered as neoadjuvant therapy prior to SOC, (surgery followed by radiation or concurrent radiochemotherapy with cisplatin 100 mg/m^2 intravenously x3) to determine if LI plus CIZ affects the 3-5 year overall survival.

Drug:
• Cyclophosphamide
Cyclophosphamide was administered IV bolus (one time only) at a dose of 300mg/m^2 three days prior to beginning treatment with LI. Standard of care (SOC) for previously untreated squamous cell carcinoma of the head and neck is currently surgery followed by radiotherapy (60-70Gy in 30 to 35 fractions over 6 to 7 weeks) for higher risk subjects (subjects determined at surgery to have adverse features per the National Comprehensive Cancer Network (NCCN) guidelines, such as, positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread, etc. that would pre-dispose them for higher risk of recurrence) radiotherapy is combined with concurrent chemotherapy (cisplatin 100mg/m^2 intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.
• Indomethacin
One 25mg capsule of indomethacin was self administered orally (BID) beginning on day one of LI treatment daily until the day before surgery.

Dietary Supplement:
• Zinc
One capsule daily self administered beginning on day one of treatment with LI until one day before surgery

Procedure:
• Surgery
Excise tumor and nodes

Drug:
• Cisplatin
Cisplatin was administered 100mg/m^2 IV concurrent with radiotherapy. The chemotherapy agent (cisplatin 100mg/m^2) was administered intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.

Radiation:
• Radiotherapy
Total 60 to 70 Gy (2Gy per day) in 30 to 35 fractions over 6 to 7 weeks to subjects determined at surgery to be at lower risk for recurrence (per NCCN guidelines). For subjects determined at surgery to be at higher risk for recurrence due to having positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread etc. (per NCCN guidelines), radiotherapy (as above) is combined with concurrent chemotherapy (cisplatin 100 mg/m^2) intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
CEL-SCI Corporation	Orient Europharma Co., Ltd., Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belarus,  Bosnia and Herzegovina,  Canada,  Croatia,  France,  Hungary,  India,  Israel,  Italy,  Malaysia,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Sri Lanka,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Interim analyses were performed (by the iDMC) periodically throughout the study to assess safety, sample size and futility.	From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
Primary	OS in Low Risk Subjects	OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Low-risk assessment and data analysis was never performed during the study and was done only after database lock.	From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary	Local Regional Control (LRC)	LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression.	From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary	LRC in Low Risk Subjects	LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression. Low risk assessment and data analysis was never performed during the study and was done only after database lock.	From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary	Progression Free Survival (PFS)	PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions.	From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary	PFS in Low Risk Subjects	PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. Low risk assessment and data analysis was not performed during the study and was performed only after database lock.	From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.
Secondary	Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 2	The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment.	Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 2
Secondary	Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 36	The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment.	Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 36
Secondary	EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 2	The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment.	Baseline [pre-randomization], Long Term Follow-up Month 2
Secondary	EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 36	The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment.	Baseline [pre-randomization], Long Term Follow-up Month 36
Secondary	Statistical Comparisons of Time-to-event Outcomes (OS, LRC, PFS) Were Repeated for Varying Levels of Histopathology (HP) Markers in Low Risk Subjects	HP analysis was performed in a blinded manner by a central pathology laboratory at the end of the study on available samples. To examine potential effects of HP markers on time-to-event efficacy outcomes (OS, LRC, PFS), participants were classified by HP marker levels: 20 HP markers were classified as (low, medium, high), 2 HP ratios as (low, medium, high) and 14 HP combinations as (low, high), resulting in 94 (20*3+2*3+2*14) possible treatment comparisons of LI + CIZ + SOC to SOC. A total of 282 (94 x 3 efficacy outcomes) statistical tests (Cox proportional hazards regressions to test for a significant treatment effect in the model) were made. Significance (two-sided p<0.05 favoring LI + CIZ + SOC) were reported under LI + CIZ + SOC. Significant test results favoring SOC were reported under SOC. The total number of statistical comparisons between LI + CIZ + SOC and SOC (282) is reported under both arms.	From the date of treatment assignment to event (LRC,PFS,OS) or the last follow-up date. Maximum follow-up was approximately 113 months.

External Links

•   Click here for more information about this study: Phase 3 Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity (IT-MATTERS)