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CTRI Number  CTRI/2024/01/061661 [Registered on: 19/01/2024] Trial Registered Prospectively
Last Modified On: 07/07/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   To Study effectiveness of oral chemotherapy with low dose immunotherapy compared with chemotherapy in Head and Neck Cancer Patients  
Scientific Title of Study   A Phase III ,Randomized controlled study comparing triple oral metronomic chemotherapy with low dose immunotherapy to intravenous chemotherapy in patients with advanced platinum sensitive head and neck squamous cell carcinoma in first line palliative setting. 
Trial Acronym  NSCLC TMCI chemo 
Secondary IDs if Any  
Secondary ID  Identifier 
version 2.0 dated 12.10.23  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Vanita Noronha 
Designation  Professor and Medical Oncologist 
Affiliation  Tata Memorial centre 
Address  OPD No 204 2nd floor Homi Bhabha Block Tata Memorial Centre Dr E Borges Marg Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769328047  
Fax    
Email  vanita.noronha@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Vanita Noronha 
Designation  Professor and Medical Oncologist 
Affiliation  Tata Memorial centre 
Address  OPD No 204 2nd floor Homi Bhabha Block Tata Memorial Centre Dr E Borges Marg Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769328047  
Fax    
Email  vanita.noronha@gmail.com  
 
Details of Contact Person
Public Query  
Name  Dr Vanita Noronha 
Designation  Professor and Medical Oncologist 
Affiliation  Tata Memorial centre 
Address  OPD No 204 2nd floor Homi Bhabha Block Tata Memorial Centre Dr E Borges Marg Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  9769328047  
Fax    
Email  vanita.noronha@gmail.com  
 
Source of Monetary or Material Support  
Tata Memorial Centre OPD No 204 2nd floor Homi Bhabha Block Dr E Borges Marg Parel Mumbai  
 
Primary Sponsor  
Name  Tata Memorial Centre 
Address  Dr E Borges Marg Parel Mumbai 400012 
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 = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Gaurav Kumar  Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur  Department of Medical Oncology, Room no 108, HBCH & RC, SKMCH Campus, Uma Nagar, Rasulpur, Muzaffarpur 842004
Muzaffarpur
BIHAR 		 9264493969

gaurav_crj@rediffmail.com 
Dr Vanita Noronha  Tata Memorial Centre  OPD No 204 2nd floor Homi Bhabha Block Tata Memorial Centre Dr E Borges Marg Parel Mumbai
Mumbai
MAHARASHTRA 		 9769328047

vanita.noronha@gmail.com 
Dr Bhavesh Poladia  Thangam Hospital and Thangam Cancer Center  Clinical Research, A Block ,Upper Basement (Room No: 1506), Thangam Hospital and Thangam Cancer Center, No: 54, Dr. Sankaran Road, Namakkal - 637001, Tamilnadu, India.
Namakkal
TAMIL NADU 		 9819151554

bhaveshpoladia@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Insituitional Ethics Committtee   Approved 
Institutional Ethics Committee  Approved 
Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C148||Malignant neoplasm of overlappingsites of lip, oral cavity and pharynx,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Cisplatin or carboplatin and paclitaxel   cisplatin 75 mg per m2 day 1 or Carboplatin area under the curve AUC 6 and paclitaxel 175 mg per m2 over 3hours on day 1 will be administered every 3 weeks till progression. 
Intervention  Triple metronomic chemotherapy with low dose nivolumab  Patients allotted to the intervention arm will receive triple metronomic chemotherapy with low dose nivolumab . TMC will consist of capsule celecoxib 200 mg twice daily, weekly methotrexate 9 mg per m2 once a week, and erlotinib 150 mg once daily, all administered orally. In addition, patients with receive intravenous nivolumab 20 mg administered in 100 mL normal saline over 60 minutes once every 3 weeks. A 21-day period will be considered a cycle . Till disease progression 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1 Subjects must have head and neck squamous cell carcinoma and must be planned
for palliative systemic therapy in the first line.
2 Patients who have received prior platinum chemotherapy in the definitive setting will be eligible as long as the disease has relapsed 6 months or beyond the time that they had received platinum therapy.
Age more than 18 years.
Eastern Cooperative Oncology Group ECOG performance status PS 0 2
3 Subjects must have normal organ and marrow function
4 Patients with HIV are potentially eligible as long as they have a CD4 count more than and equal to 200 are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS defining conditions.
5 Pregnancy test Negative serum or urine pregnancy test at screening for women of
childbearing potential.
6 Contraception Highly effective contraception for both male and female subjects throughout
the study and for at least 30 days after last nivolumab treatment administration if the risk of
conception exists. Nivolumab is teratogenic to the developing human fetus.Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately.
Willing and able to comply with all study requirements, including treatment, able to be
followed up at regular intervals and or nature of required assessments.
7Ability to understand and the willingness to sign a written informed consent document.
 
 
ExclusionCriteria 
Details  1. Subjects who are receiving any other current investigational agents.
2. IMMUNOSUPPRESSANTS Current use of immunosuppressive medication EXCEPT for the
following
a. intranasal, inhaled, topical steroids, or local steroid injection
b. Systemic corticosteroids at physiologic doses more than and equal to 10 mg per day of prednisone or equivalent
c. Steroids as premedication for hypersensitivity reactions
d. Steroids for raised intracranial pressure due to the disease itself e, Steroid use
for avoidance or treatment of emesis.
3. AUTOIMMUNE DISEASE Active autoimmune disease that might deteriorate when receiving
a chemotherapeutic agent. Patients with diabetes type I vitiligo psoriasis or hypo or
hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
4. ORGAN TRANSPLANTATION Prior organ transplantation including allogeneic stem cell
transplantation.
5. INFECTIONS Active uncontrolled infection requiring systemic therapy.
6. VACCINATION Vaccination with live viral vaccine within 4 weeks of the first dose of nivolumab and while on studyis prohibited except for administration of inactivated vaccines.
7. HYPERSENSITIVITY TO STUDY DRUG Known prior severe hypersensitivity to
platinum, paclitaxel, oral metronomic chemotherapy, or nivolumab or any component in their formulations, including known severehypersensitivity reactions to monoclonal antibodies
8. CARDIOVASCULAR DISEASE: Clinically significant cardiovascular disease
cerebrovascular accident or stroke less than 6 months prior to enrollment myocardial infarction less than 6 months prior to enrollment, unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
9. OTHER PERSISTING TOXICITIES Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy Grade 2, or other Grade 2 not
constituting a safety risk based on Investigator’s judgment is acceptable.
10. Other severe acute or chronic medical conditions including immune colitis, inflammatory
bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including
recent or active suicidal ideation or behavior; or laboratory abnormalities
that may increase the risk associated with study participation or study treatment administration
or may interfere with the interpretation of study results and, in the judgment of the Investigator,
would make the patient inappropriate for entry into this study.
11. Pregnant women are excluded from this study. Based on its mechanism of action.
nivolumab can cause foetal harm when administered to a pregnant woman. Therefore,
potential risks of administering nivolumab during pregnancy include increased rates of abortion
or stillbirth. Women of reproductive potential will be advised to use effective contraception during treatment and for at least one month after the last dose of nivolumab.
12. Lactating women There is no information regarding the presence of nivolumab in human
milk, the effects on the breastfed infant, or the effects on milk production. Since many drugs are
excreted in human milk, it is advised that a lactating woman should not breastfeed during
treatment and for at least one month after the last dose of nivolumab due to the potential for
serious adverse reactions in breastfed infants.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To assess if TMCI results in a non-inferior OS as compared to platinum-based combination chemotherapy in patients with advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting  till 5 years  
 
Secondary Outcome  
Outcome  TimePoints 
Secondary
1 To assess if TMCI leads to superior OS as compared to platinum-based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting
2 To compare the PFS from TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting
3 To compare the response rate of TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting
4 To compare the QOL of patients treated with TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting

Tertiary
To evaluate molecular parameters
 		 1 Till 5 years
2 Till 5 years
3 Every 2-3 months till progression
4 at baseline and at two monthly intervals for the first 6 months










Tertiary
Blood 10 ml will be collected at baseline, at the time of disease response evaluation& at the disease progression. 
 
Target Sample Size   Total Sample Size="422"
Sample Size from India="422" 
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 3 
Date of First Enrollment (India)   01/02/2024 
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="5"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
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  

Objective:

To evaluate the efficacy of triple oral metronomic chemotherapy with low dose immunotherapy (TMCI) over standard intravenous (IV) platinum-based chemotherapy in advanced unresectable locally advanced or metastatic HNSCC in the palliative setting.

 

Information:

The combination of oral metronomic chemotherapy with low dose immunotherapy found to be superior to oral metronomic chemotherapy alone which  has led to use of this treatment in routine care in the clinic. However, as this is not compared with IV chemotherapy with advanced HNSCC that is platinum-sensitive, would this replace  platinum-based combination chemotherapy, even in cases in which cetuximab and pembrolizumab are unaffordable is always been question discussed and both are used routinely in this setting. Therefore the TMCI regimen is proven to be non-inferior or superior to standard IV platinum-based combination chemotherapy, this will provide patients with an easily accessible, available and affordable therapeutic option.In this study 422 participants will be included in either of the standard treatment arms in ratio 1:1 by process of  randomization .Response will be assessed after every two – three months and the he response rate will be calculated as a percentage of patients having a complete response and partial response as the best response, which will be assessed in accordance with RECIST version 1.1 criteria. Duration of response will be defined as the duration in months from the first occurrence of response (complete response or partial response) until progression

Interventions (I):

Patients allotted to the intervention arm will receive triple metronomic chemotherapy with low dose nivolumab (TMCI arm). TMC will consist of capsule celecoxib 200 mg twice daily, weekly methotrexate 9 mg/m2 once a week, and erlotinib 150 mg once daily, all administered orally. In addition, patients with receive intravenous nivolumab 20 mg administered in 100 mL normal saline over 60 minutes once every 3 weeks. A 21-day period will be considered a cycle. 

 Control group (C):

CP (cisplatin 75 mg/m2 day 1or Carboplatin (area under the curve [AUC], 6 and paclitaxel 175 mg/m2 over 3hours on day 1) will be administered every 3 weeks. Carboplatin (areaunder the curve [AUC], 6) will be substituted for cisplatin in case of development of grade 2 or greater neuropathyor renal impairment (creatinine clearance< 50 mL/min), or at physician’s or patient’s choice.


Expected outcome:

If we are able to prove that TMCI is non-inferior or superior to standard IV chemotherapy, we will have established a low cost and easily accessible less toxic treatment regimen, which will benefit not just individual patients and families, but also society.

 

 
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