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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by CEL-SCI Corporation
Sponsor:
Collaborators:
Teva Pharmaceutical Industries
Orient Europharma Co., Ltd.
Information provided by (Responsible Party):
CEL-SCI Corporation
ClinicalTrials.gov Identifier:
NCT01265849
First received: December 22, 2010
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine whether LI administered in combination with cyclophosphamide, indomethacin and zinc (CIZ) in a multivitamin 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 squamous cell carcinoma of the oral cavity or soft palate at a median of 3 years


Condition Intervention Phase
Squamous Cell Carcinoma of the Oral Cavity
Squamous Cell Carcinoma of the Soft Palate
Biological: LI plus CIZ
Other: Standard of Care (SOC)
Biological: LI + SOC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by CEL-SCI Corporation:

Primary Outcome Measures:
  • Overall Survival (OS) in LI + CIZ + SOC vs. SOC [ Time Frame: 3 year ] [ Designated as safety issue: Yes ]
    OS will be assessed using Kaplan-Meier life-table and compared using a logrank test and confirmed further with tumor stage location and geographic stratified log rank tests. The unstratified logrank test constitutes the primary analysis. A two-sided p-value of 0.05 or less will be considered statistically significant for comparing the two groups. Interim analyses will be performed throughout the study to assess safety, sample size and futility.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) in LI + CIZ + SOC vs.SOC [ Time Frame: 3 year. ] [ Designated as safety issue: Yes ]
    PFS will be assessed using Kaplan-Meier life-table and compared using a logrank test and confirmed further with stage location and geographic stratified log rank tests. The unstratified logrank test constitutes the primary analysis.A two sided p-value of 0.05 or less will be considered statistically significant in comparing the groups. The Holm closed-sequential procedure will be used to control type 1 error probability to at most 0.05

  • Local regional control (LRC) in LI + CIZ + SOC vs. SOC [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    LRC is assessed by classifying the first evidence of progression in local and distal sites for the control group and for the LI treated group. LRC failure includes progression of tumor(s) and nodes or appearance of new disease above the clavicle (but not distant metastases) the reappearance of tumor in the original tumor bed, development of cervical node metastases and new disease above the clavicle other than distant metastases not present at baseline. The number and percent of subjects in the treated and untreated groups and the timing of LRC will be displayed for each group.

  • Quality of Life (QOL) in LI + CIZ + SOC vs. SOC [ Time Frame: 3 yr. ] [ Designated as safety issue: Yes ]
    QOL will be based on the EORTC QLOQ-C30 and EORTC QLQ-H&N35. QOL data will be assessed for change in QOL from baseline within and between treatment groups.Between group comparisons will be performed using ANOVA or Wilcoxon rank sum test. Within treatment group change from baseline will be performed using a paired t-test or a signed rank test. Two-sided t-test will be used with no adjustment for type I error. An exact binomial test of each treatment group will be used to assess a 10 point improvement between treatments. A Fisher Exact Test will be used for between group comparisons.


Estimated Enrollment: 880
Study Start Date: December 2010
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LI plus CIZ
LI plus CIZ is given as adjuvant therapy prior to standard of care (SOC).
Biological: LI plus CIZ
LI 400IU (2.0mL total daily) 1.0 mL peritumoral, 1.0 mL perilymphatic 5x weekly x3 weeks administered in combination with cyclophosphamide indomethacin and zinc (CIZ) as adjuvant therapy prior to SOC, surgery followed by radiation or concurrent radiochemotherapy with cisplatin 100mg/m^2 intravenously to determine if LI plus CIZ affects the overall survival of subjects at median 3 years. Cyclophosphamide 300mg/m^2 is administered intravenously bolus 3 days prior to treatment with LI. Indomethacin 25mg capsules are administered orally beginning on day 1 of LI treatment up to 1 day prior to surgery. Multivitamin tablets or capsules with zinc (> or = to 15mg but not > 40mg) are administered orally beginning on day 1 of LI treatment up to 1 day prior to surgery.
Other Names:
  • BB IND 5677
  • Multikine
  • CS001P3
Active Comparator: Standard of Care (SOC)
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery.
Other: Standard of Care (SOC)
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) or for higher risk subjects (subjects determined at surgery to have positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread) radiotherapy is combined with concurrent chemotherapy (cisplatin 100mg/m2 intravenously 1x weekly for 3 weeks on day 1 of weeks 1, 4 and 7 of radiotherapy
Other Names:
  • BB IND 5677
  • Multikine
  • CS001P3
Experimental: LI + SOC
LI is administered without CIZ to determine the contribution of CIZ to the effects of LI.
Biological: LI + SOC
LI is administered 400 IU (2.0mL) 1/2 peritumorally and 1/2 perilymphatically 5 times a week for three weeks prior to SOC to determine the contribution of CIZ on LI activity.
Other Names:
  • BB IND 5677
  • Multikine
  • CS001P3

Detailed Description:

Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US there are about 37,000 new cases annually. Ninety percent are advanced primary squamous cell carcinoma (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 combined radiochemotherapy - is between 52 and 55%; the 5 year OS is 43%. There are clearly a large number 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 1 and 2 clinical trials. LI was 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 is being 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 Arms for, Overall Survival, the Primary End Point of this Study].

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Untreated SCCHN of oral cavity/soft palate, categories T1N1-2M0,T2N1-2M0,T3N0-2M0,T4N0-2M0 (T4 allowed only if invasion of mandible is negligible) scheduled for SOC
  • Primary tumor and any positive node(s)measurable in 2 dimensions
  • normal immune function
  • no immunosuppressives with 1 year
  • KPS>70
  • Age>18
  • Male or Female (non-pregnant)
  • Life expectancy >6mo.
  • Able to take oral medication
  • Able to provide informed consent

Exclusion Criteria:

  • 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
  • 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
  • History of asthma
  • Any condition that in the opinion of the investigator would cause the subject to be unable to participate or tolerate the protocol regimen
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265849

Contacts
Contact: Eyal Talor, PhD 410-358-6866 etalor@cel-sci.com
Contact: John Cipriano, M.S. 703-506-9460 jcipriano@cel-sci.com

  Show 64 Study Locations
Sponsors and Collaborators
CEL-SCI Corporation
Teva Pharmaceutical Industries
Orient Europharma Co., Ltd.
Investigators
Study Director: Eyal Talor, PhD CEL-SCI Corporation
  More Information

Additional Information:
No publications provided

Responsible Party: CEL-SCI Corporation
ClinicalTrials.gov Identifier: NCT01265849     History of Changes
Other Study ID Numbers: CS001P3, 2010-019952-35
Study First Received: December 22, 2010
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
India: Ministry of Health
India: Institutional Review Board
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Poland: Ministry of Health
Poland: Ethics Committee
Hungary: National Institute of Pharmacy
Hungary: Scientific and Medical Research Council Ethics Committee
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Taiwan: Department of Health
Taiwan: Institutional Review Board
Ukraine: Ministry of Health
Ukraine: Ethics Committee
Serbia: Medicines and Medical Devices Agency
Croatia: Agency for Medicinal Product and Medical Devices
Bosnia and Herzegovina: Agency for Medicaments and Medical Devices

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on July 29, 2014