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
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
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"
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.