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CTRI Number  CTRI/2024/02/062244 [Registered on: 05/02/2024] Trial Registered Prospectively
Last Modified On: 26/02/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Testing the efficacy of Low-Dose Immunotherapy and Chemotherapy in patients with stage 4A or 4B cancer of the mouth 
Scientific Title of Study   A Prospective, open labelled Randomized, Multicenter, Investigator initiative Study to evaluate the Efficacy, Safety, low dose Nivolumab along with neoadjuvant chemotherapy with TPF regimen in Subjects with locally advanced stage 4A/B squamous cell carcinoma of Buccal Mucosa.  
Trial Acronym  N/A 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Satheesh Chiradoni Thungappa 
Designation  Consultant Medical Oncologist  
Affiliation  Health Care Global Enterprisers Ltd 
Address  #8, P Kalinga Rao Road,
Sampangiram Nagar
Bangalore
KARNATAKA
560027
India 
Phone  9242698750  
Fax    
Email  drsatheesh.ct@hcgel.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr B S Ajai Kumar 
Designation  Radiation Oncologist & Executive Chairman 
Affiliation  Health Care global enterprisers Ltd 
Address  #8, P Kalinga Rao Road,
Sampangiram Nagar
Bangalore
KARNATAKA
560027
India 
Phone  9845381383  
Fax    
Email  bsajaikumar@hcgel.com  
 
Details of Contact Person
Public Query
 
Name  Dr Harish Venkataravanappa Reddy  
Designation  Group Head, Medical Services 
Affiliation  Health Care Global Enterprisers Ltd 
Address  #8, P Kalinga Rao Road,
Sampangiram Nagar
Bangalore
KARNATAKA
560027
India 
Phone  7899105235  
Fax    
Email  harish.reddy@hcgel.com  
 
Source of Monetary or Material Support  
HCG Institutional Research Fund #8, P Kalinga Rao Road, Sampangiram Nagar, Bengaluru - 560027, Karnataka 
 
Primary Sponsor  
Name  HCG Institutional research Fund  
Address  # 8 P Kalinga rao road, Sampangiram Nagar, Bangalore-27  
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 11  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Srinivas K G  Bharat Hospital Institute of Oncology  Department of Medical Oncology, No. 438, Outer Ring Road, Hebbal Industrial Area Hebbal 1st Stage, Lakshmikanth Nagar, Hebbal Industrial Area, Mysuru, Karnataka 570017
Mysore
KARNATAKA 
9663121728

drsrinivas.k@bhio.org 
Dr Indoo Ambulkar  HCG Borivali  Department of Medical Oncology, Holy Cross Road, I C Colony, Off. Borivali Dahisar, New Link Rd, Borivali, W, 400092
Mumbai (Suburban)
MAHARASHTRA 
9870041463

drindoo.a@hcgel.com 
Dr Pinaki Mahato  HCG Cancer Center Vadodara  Department of Medical Oncology, Sun-Pharma Atladra Rd, Pramukh Swami nagar, Atladara, Vadodara, Gujarat - 390012
Vadodara
GUJARAT 
9998974704

pinaki.mahato@hcgel.com 
Dr Sanketh Kotne  HCG Cancer Center Vizag  Department of Medical Oncology, Pinnacle Hospital Compound, APIIC Health City, Arilova, Chinnagadili, Andhra Pradesh 530040
Visakhapatnam
ANDHRA PRADESH 
7013222831

drsanketh.k@hcgel.com 
Dr Kaustubh Patel  HCG Cancer Center, Ahmedabad  Department of Head and Neck Surgical Oncology. Sola-Science City Road, Off S.G. Highway, Sola, Ahmedabad, Gujarat 380060
Ahmadabad
GUJARAT 
9825289089

kaustubhpatel19@gmail.com 
Dr Satheesh Chiradoni Thungappa  HCG Cancer Center, Bangalore  Department of Medical Oncology, Tower 1, First Floor, #8, P Kalinga Rao Road, Sampangiram Nagar, Bangalore-27
Bangalore
KARNATAKA 
9242698750

drsatheesh.ct@hcgel.com 
Dr Naresh Somani  HCG Cancer Center, Jaipur  Department of Medical Oncology, Jaipur Shipra path Mansarovar, Jaipur - 302020
Jaipur
RAJASTHAN 
9829014996

drnaresh.s@hcgel.com 
Dr Nandish Kumar  HCG Cancer Center, Kalaburagi  Department of Medical Oncology, No.1-10, A, 1-10, Station Rd, Khuba Plot, Brhampur, Gulbarga, Karnataka 585105
Gulbarga
KARNATAKA 
7259029517

drnandish.j@hcgel.com 
Dr K L Priyadarshini  HCG Curie City Cancer Center Vijayawada  Department of Medical Oncology, 29-19-19, Dornakal Rd, Moghalrajpuram, Suryaraopeta, Governor Peta, Vijayawada, Andhra Pradesh 520002
Krishna
ANDHRA PRADESH 
9966030988

drlakshmi.p@hcgel.com 
Dr Shantanu Pendse  HCG NCHRI Cancer Center  Department of Medical Oncology, Mouja Wanjri Khasra No.50, 51 Ring Road Near Automotive Square Kalam Bande Nawaz Nagar, Binaki, Nagpur, Maharashtra 440017
Nagpur
MAHARASHTRA 
8600863057

drshantanu.s@hcgel.com 
Dr Srigopal Mohanty  HCG Panda Cancer Hospital  Department of Medical Oncology, HCG Panda Cancer Hospital, NH – 16, Telengapentha, Cuttack, Odisha – 754001
Cuttack
ORISSA 
8731959346

dr.srigopal@hcgel.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 11  
Name of Committee  Approval Status 
BHIO Ethics Committee  Approved 
HCC Vadodara Ethics Committee  Submittted/Under Review 
HCG Cancer Center - Institutional Ethics Committee  Approved 
HCG Cancer Center Institutional Ethics Committee  Approved 
HCG Curie City Cancer Center Institutional Ethics Committee  Approved 
HCG Multispecialty Ethics Committee  Approved 
HCG NCHRI IEC  Approved 
HCG-Central Ethics Committee  Approved 
HCGEL Jaipur Institutional Ethics Committee  Submittted/Under Review 
IEC HCG Cancer Center Vizag  Approved 
Institutional Ethics Committee - HCG Panda Cancer Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C060||Malignant neoplasm of cheek mucosa,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Docetaxel, Cisplatin, Fluorouracil  Docetaxel Intraperitoneal Day 1, Day 22, Day 43 Cisplatin Intraperitoneal Day 1, Day 22, Day 43 Fluorouracil Intraperitoneal Day 1, Day 22, Day 43 
Intervention  Nivolumab, Docetaxel, Cisplatin, Fluorouracil  Nivolumab Intraperitoneal 40mg Day 1, Day 15, day 29 Docetaxel Intraperitoneal Day 1, Day 22, Day 43 Cisplatin Intraperitoneal Day 1, Day 22, Day 43 Fluorouracil Intraperitoneal Day 1, Day 22, Day 43 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  Subject age 18 to 70 yrs
Either male or female
Histologically or cytologically documented squamous cell carcinoma of Buccal mucosa
Locally advanced (T3-T4,N2-N3, M0) (Stage IVa, IVb)
subject if fit to take TPF neoadjuvant chemotherapy
 
 
ExclusionCriteria 
Details  1. Subjects with Head and neck cancer with Squamous cell carcinoma other than Buccal mucosa or Buccal mucosa with any distant metastatic disease
2. Non squamous cell carcinoma HPE or Salivary gland tumors or Nasopharyngeal tumors
3. History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti- HCV at Screening
4. History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
5. Other active malignancy requiring concurrent intervention.
6. Subject with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to screening AND no additional therapy is required or anticipated to be required during the study period.
7. Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
8. Subject with active, known or suspected autoimmune disease. Subject with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
9. Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents
10. Prior radiotherapy or radiosurgery received within 2 weeks prior to screening.
11. Prior treatment with Nivolumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD-137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
12. Subject with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
13. Recent cardiac illness myocardial infarction within 6 months
14. Subject not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
15. History of severe hypersensitivity reactions to other monoclonal antibodies.
16. Allergy or intolerance (unacceptable adverse event) to study drug components, or Polysorbate-80-containing infusions
17. Ongoing or planned administration of anti-cancer therapies other than those specified in this study or use of strong CYP3A4 inhibitors.
18. Have received treatment with any other investigational drug in the last 30 days before study entry, or within less than five half-lives after receiving the previous investigational drug.
19. Receipt of IV antibiotics for infection within 14 days of randomization

20. Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment.
21. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
22. Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment or any other medical or psychiatric condition that could compromise study participation.
23. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at Screening if required as per medical history.
24. Have any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Overall Response Rate  9 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
Pathological response
Disease Free Survival
Overall Survival
Safety
Quality of life 
Disease Free Survival at 6,12,18,24 months
Overall Survival at 6,12,18,24 months
 
 
Target Sample Size   Total Sample Size="50"
Sample Size from India="50" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   12/02/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="8"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Subjects with Head and neck cancer with Squamous cell carcinoma other than Buccal mucosa or Buccal mucosa with any distant metastatic disease

Non squamous cell carcinoma HPE or Salivary gland tumors or Nasopharyngeal tumors

History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti- HCV at Screening

History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening

Other active malignancy requiring concurrent intervention.

Subject with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to screening AND no additional therapy is required or anticipated to be required during the study period.

Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Subject with active, known or suspected autoimmune disease. Subject with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents

Prior radiotherapy or radiosurgery received within 2 weeks prior to screening.

Prior treatment with Nivolumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD-137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

Subject with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

Recent cardiac illness myocardial infarction within 6 months

Subject not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.

History of severe hypersensitivity reactions to other monoclonal antibodies.

Allergy or intolerance (unacceptable adverse event) to study drug components, or Polysorbate-80-containing infusions

Ongoing or planned administration of anti-cancer therapies other than those specified in this study or use of strong CYP3A4 inhibitors.

Have received treatment with any other investigational drug in the last 30 days before study entry, or within less than five half-lives after receiving the previous investigational drug.

Receipt of IV antibiotics for infection within 14 days of randomization  

 

Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment.

Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)

Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment or any other medical or psychiatric condition that could compromise study participation.

History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at Screening if required as per medical history.

Have any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

 
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