| CTRI Number |
CTRI/2011/05/001716 [Registered on: 06/05/2011] Trial Registered Prospectively |
| Last Modified On: |
20/11/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Biological |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
Public Title of Study
Modification(s)
|
A Phase III Study of the Effects of Multikine on Cancer of the Oral Cavity. |
Scientific Title of Study
Modification(s)
|
A Phase III, Open-label, Randomized, Multi-center Study of the Effects of Leukocyte Interleukin, Injection [Multikine] Plus Standard of Care (Surgery + Radiotherapy or Surgery + Concurrent Chemoradiotherapy) in Subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity / Soft Palate Versus Standard of Care Only |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Registry |
| CS001P3 |
Protocol Number |
| NCT01265849 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details Contact Person
Scientific Query
Modification(s)
|
| Name |
Sanjay Kabra |
| Address |
Unit 1101, Level 11, Millenia Tower B
1&2 Murphy Road
Bangalore
KARNATAKA
560 008
India |
| Phone |
91-22-40957342 |
| Fax |
91-22-40957399 |
| Email |
SKabra@pharmanet.com |
|
Details Contact Person
Public Query
Modification(s)
|
| Name |
Sanjay Kabra |
| Address |
Unit 1101, Level 11, Millenia Tower B
1&2 Murphy Road
Not Applicable
N/A
560 008
India |
| Phone |
22-40957342 |
| Fax |
22-40957399 |
| Email |
SKabra@pharmanet.com |
|
Source of Monetary or Material Support
Modification(s)
|
| CEL-SCI Corporation; 8229 Boone Boulevard, Suite 802
Vienna, Virginia 22182 U.S.A.
|
|
Primary Sponsor
Modification(s)
|
| Name |
CELSCI Corporation |
| Address |
8229 Boone Boulevard, Suite 802Vienna, Virginia 22182 U.S.A. |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
|
Countries of Recruitment
Modification(s)
|
Canada
Hungary
India
Israel
Poland
Russian Federation
Taiwan
Ukraine
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 14 |
| Contact Person |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Subramania Iyer |
Amrita Institute of Medical Sciences |
Department of Oncology,Ponekkara,-682041
Ernakulam
|
914842801234
914842802082
iyersubu@gmail.com |
| Dr Suresh Attili |
Bibi General Hospital and Cancer Centre |
Department of Medical Oncology, 16-3-991-1-C, Government Printing Press Road, Malakpet, Hyderabad - 500024.
Hyderabad
|
91-40-23319999
91-40-23370655
sureshattili@yahoo.com |
| Dr Braj Raj Shrivastava |
Cancer Hospital and Research Centre |
Department of Oncology,Cancer Hill, Mandre Ki Mata, -474009
Gwalior
|
919425109174
917512336506
br_shrivastav08@yahoo.com |
| Dr Rajnish Vasant Nagarkar |
Curie Manavata Cancer Centre |
Department of Oncology,Opposite Mahamarg Bus Stand, Mumbai Naka, -422004
Nashik
|
919823061929
912532592666
drrajnagarkar@yahoo.co.in |
| Dr Dinesh Singh |
Galaxy Cancer Center |
Department of Radiation Oncology, Galaxy Cancer Center, Pushpanjali Crosslay Hospital,
W 3, Sector 1, Vaishali,
Ghaziabad 210 010, Uttar Pradesh, India
Ghaziabad
|
911204173865
911204173865
drdineshsingh@hotmail.com |
| Dr Balaji Keshavrao Shewalkar |
Government Medical College and Hospital |
Department of Radiotherapy and Oncology,Panchakki Road, -431001
Aurangabad
|
912402400640
912402400640
bkrish@rediffmail.com |
| Dr Sanjeev Misra |
King Georges Medical University/Chhatrapati Shahuji Maharaj (CSM) Medical University |
Department of Surgical Oncology King George’s Medical University Chhatrapati Shahuji Maharaj Medical University 226003
Lucknow
|
915223240428
915222255346
misralko@gmail.com |
| Dr. Kirushna Kumar, Kosanam Subramanian |
Meenakshi Mission Hospital & Research Center |
Department of Radiation Oncology,Lake Area, Melur Road,-625107
Madurai
|
91 9787713004 / 9842113003
91 452 4219030
drkskk@yahoo.com |
| Dr Rejnish Kumar |
Regional Cancer Centre |
Department of Head and Neck,Medical College Campus, P O Box 2417,-695011
Thiruvananthapuram
|
914712522384
914712443814
rejnish@yahoo.com |
| Dr Anish Maru |
Searoc Cancer Center |
Department of Oncology, S K Soni Hospital,,Sector 5, Vidhyadhar Nagar, Sikar Road,-302013
Jaipur
|
919829060128
911412233337
anishmaru@yahoo.com |
| Dr DharamPal Singh Gurawa |
SMS Medical College and Attached Hospitals |
Dept. of Radiotherapy and Oncology,,Sawai Ram Singh Road, -302004
Jaipur
|
911412518478
911412518478
drdpsingh@yahoo.com |
| Dr. Rajendersingh Sujansingh Arora |
Sujan Surgical Cancer Hospital and Amravati Cancer Foundation |
Department of Oncology, ,52/B, Shankar Nagar, Main Road,-444606
Amravati
|
91 721 2671496 / 91 9823097573
91 721 2578568
rsaroradr@gmail.com |
| Dr. Devendra Arvind Chaukar |
Tata Memorial Hospital |
Department of Head and Neck Services,Dr. E Borgas Road, Parel,-400012
Mumbai
|
91 22 24177000
91 22 24146937
dchaukar@rediffmail.com |
| Dr Murugaiyan Nagarajan |
V. N. Cancer Centre, G. Kuppuswamy Naidu Memorial Hospital |
Department of Radiation Oncology,Post Box. No. 6327, Nethaji Road, Pappanaikenpalayam, -641037
Coimbatore
|
919894016715
914222245756
mnr81@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 11 |
| Name of Committee |
Approval Status |
| Amravati Ethics Committee, Sujan Surgical Cancer Hospital and Amravati Cancer Foundation |
Approved |
| BIBI Institutional Ethics Committee, Bibi General Hospital and Cancer Centre. |
Approved |
| Ethical Review Board, Meenakshi Mission Hospital & Research Centre |
Approved |
| Human Ethics Committee, Regional Cancer Center |
Approved |
| Human Ethics Committee, Tata Memorial Hospital |
Approved |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences and Research Centre |
Approved |
| Institutional Ethics Committee, Cancer Hospital & Research Institute |
Approved |
| Institutional Ethics Committee, GKNM Hospital |
Approved |
| Institutional Ethics Committee, Government Medical College |
Approved |
| Institutional Ethics Committee, Pushpanjali Crosslay Hospital |
Approved |
| Manavata Clinical research Institute- Professional Ethics Committee |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Advanced Primary Squamous Cell Carcinoma of the Oral Cavity / Soft Palate Versus Standard of Care Only |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Leukocyte Interleukin, Injection [Multikine] |
Total daily dose: 400 IU (as IL-2), 5x/week for 3 weeks. |
| Intervention |
Leukocyte Interleukin, Injection [Multikine] + CIZ |
Total daily dose: 400 IU (as IL-2), 5x/week for 3 weeks.
CIZ: Cyclophosphamide 300 mg/m2 (x1,IV bolus, Day -3); Indomethacin 25mg tid, po (Day 1 to approximately 24 hrs prior to surgery) + Zinc (as Multivitamin) po id (daily, from Day 1 to approximately 24 hours prior to surgery )
|
| Comparator Agent |
Standard of Care |
Surgery + Radiotherapy or Surgery + Concurrent Chemoradiotherapy |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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
|
|
| ExclusionCriteria |
| Details |
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
|
|
Method of Generating Random Sequence
Modification(s)
|
Computer generated randomization |
Method of Concealment
Modification(s)
|
Not Applicable |
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| 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. |
Overall Survival (OS) in LI + CIZ + SOC vs. SOC [Time Frame: 3 year]. |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Local regional control in (Leukocyte Interleukin) + (Cyclophosphamide, Indomethacin, Zinc) + (Standard of Care) vs. (Standard of Care) [Designated as safety issue: Yes] |
[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] |
[Time Frame: 3 year.] |
Quality of Life in (Leukocyte Interleukin) + (Cyclophosphamide, Indomethacin, Zinc) + (Standard of Care) vs. (Standard of Care)
[Designated as safety issue: Yes]
|
[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. |
NIL |
|
Target Sample Size
Modification(s)
|
Total Sample Size="880"
Sample Size from India="230" |
Phase of Trial
Modification(s)
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
20/05/2011 |
| Date of First Enrollment (Global) |
07/01/2011 |
Estimated Duration of Trial
Modification(s)
|
Years="5"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
Publication Details
Modification(s)
|
NA |
Brief Summary
Modification(s)
|
This is a Phase III, open-label, randomized, multi-center study of Multikine given peri-tumorally and peri-lymphatically to subjects with cancer of the oral cavity and soft palate scheduled for surgical excision of tumor followed by radiotherapy or chemoradiotherapy. Subjects will be randomized in a 3:1:3 ratio to one of the 3 groups : Group 1 (Multikine + CIZ + SOC), Group 2 (Multikine + SOC) and Group 3 (SOC only). Subjects randomized to one of the Multikine treatment groups (Group 1 and Group 2) will receive Multikine, 400 IU (2 mL) is injected each day of study drug administration, 1/2 dose (1 mL) peri-tumorally and 1/2 dose (1 mL) peri-lymphatically at the jugular lymphatic chain ipsilaterally to the injected tumor site inferior to the tip of the mastoid process in the area of the sternomastoid muscle sequentially and during the same visit. Both injections (peri-tumorally and peri-lymphatically) are administered 5 times per week for 3 weeks. Subjects in Group 2 will also receive receive 300 mg/m2 cyclophosphamide (IV bolus on Day minus 3 of first Multikine injection) and 25 mg indomethacin (tid po daily with food from Day 1 to one day prior to surgery). Additionally, a multivitamin supplement containing zinc is given from Day 1 to the day before surgery for immune system/nutritional support. Subjects in Group 3 will received only Standard of care (SOC) i.e surgery followed by radiotherapy or concurrent chemoradiotherapy. All subjects in the high-risk group as defined in the protocol definition ’High-Risk’, will also receive 100mg/m2 intravenously (IV) 1x/wk weeks 1, 4 and 7 (or Day 1, 22, 43 of start of radiotherapy course). |
