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CTRI Number  CTRI/2023/12/060746 [Registered on: 26/12/2023] Trial Registered Prospectively
Last Modified On: 05/02/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Single Arm Study 
Public Title of Study   To evaluate if NRC-2694-A and Paclitaxel is safe and will reduce the tumor size for recurrent/metastatic Head and Neck cancer patients who fail to respond ICI therapy.  
Scientific Title of Study   A Phase 2 Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination with Paclitaxel in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NCT05283226  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Suresh H Advani 
Designation  Medical Oncologist 
Affiliation  Daycare Angels Under AOH, Sushrut Hospital and Research Centre  
Address  Daycare Angels Under AOH, 3rd Floor, Sushrut Hospital and Research Centre, 365, Swastik Park, Chembur East, Mumbai

Mumbai
MAHARASHTRA
400071
India 
Phone    
Fax    
Email  Sushrut.hospital18@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Praveen C Myneni 
Designation  Medical Officer  
Affiliation  NATCO Pharma Ltd 
Address  NATCO Pharma Ltd NATCO House, Road No. 2, Banjara Hills, Hyderabad

Hyderabad
TELANGANA
500034
India 
Phone  04023547532  
Fax    
Email  Drpraveen@natcopharma.co.in  
 
Details of Contact Person
Public Query  
Name  Dr G Venkat Ramana 
Designation  Principal Scientist  
Affiliation  NATCO Pharma Ltd 
Address  NATCO Pharma Ltd, NATCO House, Road No 2, Banjara Hills, Hyderabad

Hyderabad
TELANGANA
500034
India 
Phone  04023547532  
Fax    
Email  gvramana@natcopharma.co.in  
 
Source of Monetary or Material Support  
NATCO Pharma Limited, NATCO House, Road No. 2, Banjara Hills, Hyderabad - 500 034 
 
Primary Sponsor  
Name  NATCO Pharma Limited 
Address  NATCO House, Road No. 2, Banjara Hills, Hyderabad - 500 034 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     United States of America
India  
Sites of Study
Modification(s)  
No of Sites = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr M V T Krishna Mohan  Basavatarakam Indo American Cancer Hospital & Research Institute  Road No. 10, Banjara Hills, Hyderabad - 500034
Hyderabad
TELANGANA 		 9866154503
040-23550015
mvtkm@yahoo.com 
Dr Minish Jain  Ruby Hall Clinic  Grant Medical Foundation Ruby Hall Clinic, Cancer Care Division, Medical Oncology Department, 40, Sassoon Road, Pune-411001
Pune
MAHARASHTRA 		 9823133390

minishjain009@gmail.com 
Dr Suresh H Advani  Sushrut Hospital and Research Centre  Daycare Angels, Oncology Department, Oncology Division, 3rd Floor, 365, Swastik Park, Chembur (East) , Mumbai 400071
Mumbai
MAHARASHTRA 		 9821157706

shadvani2000@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Institutional Ethics Committee  Approved 
Institutional Ethics Committee Poona Medical Research Foundation  Approved 
Mumbai Oncocare Centre Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
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  NA  As this is a single arm study. There is no comparator. 
Intervention  NRC-2694-A and Paclitaxel  1. NRC-2694-A 300 mg once daily will continue until disease progression or intolerable toxicity due to the drug, whichever occurs first. 2. Paclitaxel 175 mg/m2 IV once in 21 days cycle 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1. Is willing and capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
2. Is male or female aged 18 years or older at the time of consent.
3. Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx, hypopharynx, and larynx).
4. Has documented radiographical progressive disease assessed by the investigator per RECIST v1.1.
5. Has a measurable lesion per RECIST v1.1.
6. Has ECOG performance status score of ≤2.
7. Must have progressed during or after receiving ICI therapy, such as pembrolizumab or nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg, pembrolizumab or nivolumab) and who had recovered prior to study entry will also be eligible.
8. Female patients of childbearing potential should have a negative urine test before enrollment. If the urine pregnancy test is positive or gives equivocal results, a serum pregnancy will be required for confirmation.
9. Patients of reproductive age must use acceptable methods of contraception throughout the study period and for 30 days following the last dose of investigational product (see Section 6.5.1 for further guidance).
10. During screening and at subsequent visits, the investigator should ensure adequate bone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, and hemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥50 mL/min calculated by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 × ULN [except patients with documented Gilbert’s syndrome] and serum transaminase levels ≤2.5 × ULN or ≤5 × ULN for liver metastasis and/or obstructive jaundice).
11. Must have completed a duration of at least 4 weeks after stopping ICI therapy and must have recovered to grade ≤1 from all toxicities due to this therapy. 
 
ExclusionCriteria 
Details  1. Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lung disease, renal or psychiatric disorders, not controlled with therapy corresponding to
the illness or a condition that contraindicates the use of a taxane or an EGFR inhibitor.
2. Has uncontrolled brain metastases. Patients are allowed if brain metastasis has been previously treated with surgery, whole brain irradiation, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of
prednisone or equivalent) at the time of the first dose of investigational product. Radiological evaluation of brain metastasis will be performed only if the patient has symptoms. For asymptomatic patients, brain imaging during screening is not required.
3. Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval >480 milliseconds [CTCAE grade 1] using Fridericia’s QT correction formula).
4. Has a history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
5. Has had prior cetuximab therapy for recurrent or metastatic disease. Note that cetuximab used concomitantly with radiotherapy or as an induction therapy is acceptable.
6. Has received any other EGFR-targeted therapies for recurrent or metastatic disease.
7. Currently participating in any clinical trial or receiving investigational therapy on expanded access or compassionate basis.
8. Has nasopharyngeal carcinomas or salivary gland cancers.
9. Has received investigational products or any other salvage therapy after failure of pembrolizumab/nivolumab therapy.
10. Female patient who tested positive for pregnancy.
11. Female patient who is breastfeeding or planning to become pregnant, or male patient planning to father a child within the duration of the study.
12. Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However, patients who test positive for HCV antibody, but negative for HCV RNA, will be allowed. In addition, patients with controlled HIV, chronic HBV on suppressive antiviral therapy, or a history of HCV infection status post-curative
antiviral treatment with an HCV viral load below limit of quantification are permitted to participate (DHHS 2020).
13. Has active infection requiring intravenous anti-infective therapy within 7 days prior to Day 1 Cycle 1 or is febrile due to infection.
14. Has had major surgery within 4 weeks prior to screening.
15. Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 or anticipation that such a live attenuated vaccine will be required during the study.
16. Has known or suspected hypersensitivity to any components of the formulation used for this investigational product.
17. Has concurrent disease or any clinically significant abnormality following the investigator’s review of the screening physical examination findings, 12-lead ECG results, and clinical laboratory tests, which in the judgment of the investigator would
interfere with the patient’s participation in this study or evaluation of study results.
18. Unable to come for study visits per schedule.
19. Has current drug or alcohol abuse.
20. Has received prior treatment with paclitaxel or docetaxel for metastatic or recurrent HNSCC. However, prior paclitaxel or docetaxel as a component of a curatively intended multimodality treatment for locally advanced HNSCC is permitted. 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Objective response in terms of CR/PR per RECIST v1.1  Cycle 1 Day 1, Cycle 3, Cycle 5, Monotherapy and End of Treatment. 
 
Secondary Outcome  
Outcome  TimePoints 
1. To evaluate the PFS, OS, DoR, and CBR of patients
treated orally with NRC-2694-A in combination with
paclitaxel.
2. To evaluate the safety of NRC-2694-A in combination
with paclitaxel.
3. To characterize the PK of NRC-2694-A after repeated
oral doses.
4. To determine the association between NRC-2694-A
activity and biomarkers in blood samples. 		 Cycle 1 Day 1, Cycle 3, Cycle 5, Monotherapy and End of Treatment. 
 
Target Sample Size   Total Sample Size="46"
Sample Size from India="20" 
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)   03/01/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  21/12/2022 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Open to Recruitment 
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  
Title: A Phase 2 Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination with Paclitaxel in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy.

Objectives: 
Primary
  • To determine if NRC-2694-A administered orally in combination with paclitaxel demonstrates objective response in patients with R/M HNSCC, who have had radiological progression on or after treatment with ICI therapies like pembrolizumab or nivolumab.
Secondary
  • To evaluate the PFS, OS, DoR, and CBR of patients treated orally with NRC-2694-A in combination with paclitaxel
  • To evaluate the safety of NRC-2694-A in combination with paclitaxel
  • To characterize the PK of NRC-2694-A after repeated oral doses 
Exploratory
  • To determine the association between NRC-2694-A activity and biomarkers in blood samples.
Study Design: This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy. A total of approximately 46 male and female patients will be enrolled. This sample size is based on Simon’s 2-stage design with historical control ORR of 30% and a target ORR of 50%.

Efficacy Assessments:
Response to the treatment will be assessed using RECIST v1.1. Contrast MRI/CT will be performed to the measurable lesion at the timepoints specified. In addition to MRI/CT scan, whole body FDG-PET scan will be performed during screening. The investigator will decide if further FDG-PET imaging is required to assess the progressive disease. Radiological assessment/review will be investigator-based.

Safety Assessments:
Safety assessments to be performed include physical examination, vital sign measurements (blood pressure, heart rate, respiratory rate, and oral body temperature), ECOG, clinical laboratory analyses (hematology, biochemistry, and urinalysis will be done locally), ECG, AEs (including SAEs and AESIs), and pregnancy testing throughout the study. Adverse events will be graded according to NCI CTCAE version 5.0.
 
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