A Phase III Study of the Effects of Multikine on Cancer of the Oral Cavity.

Phase 3

Conditions: Health Condition 1: null- Advanced Primary Squamous Cell Carcinoma of the Oral Cavity / Soft Palate Versus Standard of Care Only

Registration Number: CTRI/2011/05/001716

Lead Sponsor: CELSCI Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Closed to Recruitment of Participants

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1 Previously untreated primary squamous cell carcinoma of the oral cavity inclusive of the tongue but not the base of the tongue floor of the mouth cheek buccal mucosa and soft palate only confirmed by biopsy with or without regional lymph nodal metastases deemed curable by and scheduled for definitive treatment by surgical resection and postoperative radiation therapy or surgical resection and postoperative concurrent chemoradiotherapy standard of care Tumors in other locations and those in other locations of the head and neck are excluded The primary tumor class must be T1 T2 or T3 and must NOT measure more than 6 cm in greatest dimension T4 is allowed if invasion of the Mandible is minimal defined as less than0 5cm as confirmed by CT andor MRI with the use of CT imaging being mandatory and can be salvaged by marginal mandiblectomy retention of function and having intact mandible post surgery The class of clinically positive lymph node s must be N1 or N2 and must not measure more than 6 cm in greatest dimension Clinical tumor stage must be III or IV For stage IV only subjects treatable by surgical resection or surgical resection followed by postoperative radiation radiochemotherapy are eligible

Eligible TNM Categories

T1 N1 2 M0

T2 N1 2 M0

T3 N0 2 M0

T4 N0 2 M0

T4 is allowed if invasion of the mandible is minimal defined as less than point 5cm as confirmed by CT and or MRI with CT imaging mandatory and can be salvaged by marginal mandiblectomy retention of function and having intact mandible post surgery

2 Primary tumor and if present clinically positive lymph nodes with at least one measurable lesion as defined by the RECIST criteria and measurable in two dimensions by physical examination

3 greater than or equal to 18 years of age

4 If female is neither pregnant nor lactating

5 If subject is of reproductive potential they must be willing and able to utilize effective methods of contraception e g barrier methods with spermicide

6 Hemoglobin greater than 9gm dL WBC greater than 3000 mm3 platelets greater than 100 000 mm3 bilirubin less than 1 0 mg dL creatinine less than 1 2 mg dL

7 No prior therapy with IL 2 IL 1 or any other biological response modifier e g interferon alpha beta or gamma GCSF GMCSF in past one year

8 Negative reaction to intradermal test with ciprofloxacin a fluoroquinolone antibiotic

9 No immune depressive drugs e g corticosteroids cyclosporine methotrexate or anticancer agents in past one year Subjects on topical corticosteroids to treat dermatological conditions covering not more than 5 percentage of body surface area are considered eligible 10 Life expectancy greater than six months

11 Karnofsky score 70 or greater

12 Able to take oral medication

13 Able to provide informed consent

14 Must have normal immune function i e must not be known to be HIV infected or have any other disease or condition causing significant immunodeficiency

Exclusion Criteria

1 Subjects other than those to be treated by surgery followed by radiation therapy plus minus chemotherapy

2 Tumor invasion of bone as detected by a suitable imaging technique MRI and or CT or by physical examination except for mandibular invasion as described above for T4 Tumor

3 Any T1N0 or T2N0 stage tumors and all tumors classified as T4 N3 and or any TN classification with M1 or greater

Note only M0 is allowed in this study or in locations other than those specified in Inclusion Criteria 1

4 Prior history of and treatment for peptic ulcer with ongoing evidence of peptic ulcer

5 Prior surgical resection of the jugular lymph nodes on the ipsilateral neck that the injection is to be administered

6 Any acute or chronic viral bacterial immune or other disease in a stage usually associated with abnormal cellular immunity e g HIV infection hepatitis nephritis lung disease rheumatoid arthritis or other autoimmune disease

7 Subjects on hemodialysis or peritoneal dialysis

8 Prior history of asthma

9 Prior completion of one or more courses of therapeutic irradiation excluding such treatment of the extremities

10 History of allergic reaction to fluoroquinolone antibiotics e g ciprofloxacin ofloxacin

11 History of any other malignancy excluding basal cell carcinoma of the skin and in situ carcinoma of the cervix

12 History of congestive heart failure CHF and other heart conditions that in the opinion of the investigator would cause the subject to likely be unable to participate in the study or tolerate the studies protocol regimen including the surgical procedure

13 The opinion of the investigator that the subject may be unable to tolerate the protocol regimen or that participation in the trial may compromise the subjects preparation for tumor treatment

14 Failure to meet the Inclusion Criteria

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.Timepoint: Overall Survival (OS) in LI + CIZ + SOC vs. SOC [Time Frame: 3 year].

Secondary Outcome Measures

Name	Time	Method
ocal regional control in (Leukocyte Interleukin) + (Cyclophosphamide, Indomethacin, Zinc) + (Standard of Care) vs. (Standard of Care) [Designated as safety issue: Yes]Timepoint: [Time Frame: 2 years];Progression Free Survival in (Leukocyte Interleukin) + (Cyclophosphamide, Indomethacin, Zinc) + (Standard of Care) vs. (Standard of Care)[Designated as safety issue: Yes]Timepoint: [Time Frame: 3 year.];Quality of Life in (Leukocyte Interleukin) + (Cyclophosphamide, Indomethacin, Zinc) + (Standard of Care) vs. (Standard of Care) <br/ ><br>[Designated as safety issue: Yes] <br/ ><br>Timepoint: [Time Frame: 3 yr.];To evaluate the effects of Multikine treatment on the cumulative incidence of loco-regional control, progression-free survival, tumor response, tumor histopathology, and quality of life, while confirming Multikine safety.Timepoint: NI