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CTRI Number  CTRI/2022/06/043203 [Registered on: 13/06/2022] Trial Registered Prospectively
Last Modified On: 30/05/2023
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   A study to evaluate the safety and efficacy of test product TK-90 or placebo in Head and Neck cancer patients receiving radiotherapy.  
Scientific Title of Study   A Phase 2a, multi-center, placebo-controlled, randomized, assessor-blind study to assess the safety & efficacy of parenteral TK-90 or parenteral TK-90 placebo administered daily to Patients scheduled to receive radiotherapy for non-metastatic squamous cell carcinoma of the head and neck (SCCHN). 
Trial Acronym  TOSK 0004  
Secondary IDs if Any  
Secondary ID  Identifier 
CLP-2690-0004 Protocol Version 1.0 Dated 16-Feb-2022  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sagar Bhosale  
Designation  Managing Director 
Affiliation  TOSK, INC 
Address  TOSK, INC. 179/176 (I), Alto Bella Vista, Sangolda, Porvorim, Goa, India - 403521

Thane
MAHARASHTRA
403521
India 
Phone  91-7989955147  
Fax    
Email  sbhosale@tosk.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Ganesh Divekar 
Designation  Vice President - Clinical Operations, Biometrics & Medical Services 
Affiliation  SIRO Clinpharm Pvt. Ltd. 
Address  SIRO Clinpharm Pvt. Ltd. Kalpataru Prime, 1st floor, Unit Nos. 3 & 4, Plot no. D3,Road no. 16, Wagle Industrial Estate, Thane (W) - 400 604, Maharashtra, India.

Thane
MAHARASHTRA
400604
India 
Phone  02261088000  
Fax  02261088081  
Email  ganesh.divekar@siroclinpharm.com  
 
Details of Contact Person
Public Query  
Name  Dr Ganesh Divekar 
Designation  Vice President - Clinical Operations, Biometrics & Medical Services 
Affiliation  SIRO Clinpharm Pvt. Ltd. 
Address  SIRO Clinpharm Pvt. Ltd. Kalpataru Prime, 1st floor, Unit Nos. 3 & 4, Plot no. D3,Road no. 16, Wagle Industrial Estate, Thane (W) - 400 604, Maharashtra, India.


MAHARASHTRA
400604
India 
Phone  02261088000  
Fax  02261088081  
Email  ganesh.divekar@siroclinpharm.com  
 
Source of Monetary or Material Support  
Tosk, Inc. 
 
Primary Sponsor  
Name  Tosk Inc 
Address  2672 Bayshore Parkway, Suite 507 Mountain View, CA 94043 USA  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 6  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Neha Gupta  Apex Hospital Varanasi  CRC Room, 1st floor, D.L.W. Hydle Road , Varanasi-221004, Uttar Pradesh
Varanasi
UTTAR PRADESH 		 8004354185

drneha_500@yahoo.com 
Dr Aruna R   Bangalore Medical college and Research Institute  #66 & 67/A, First floor, Department of Medicine, Medicine C Block, BMCRI, Fort, KR Road Bangalore-560002, Karnataka
Bangalore
KARNATAKA 		 9535569903

arunadr2006@gmail.com 
Dr Anupam Datta  Netaji Subhash Chandra Bose Hospital  Department of Clinical Research, Upper Basement 3081, Nayabad, New Garia, Kolkata-700094, West Bengal, India
Kolkata
WEST BENGAL 		 9163067435

dranupamdatta@gmail.com 
Dr B Ravi Shankar  Omega Hospitals  Plot no 4, Health city, Chinagadili, Arilova, Hanumanthawaka, Visakhapatnam-530040, Andhra Pradesh
Visakhapatnam
ANDHRA PRADESH 		 9849123256

dr.bellalaravishankar@gmail.com 
Dr Anita Ramesh  Saveetha Medical College and Hospital  Saveetha University, Saveetha Nagar, Thandalam, Chennai Tamilnadu 602105
Chennai
TAMIL NADU 		 9840758567
04466726623
anitachandra100@hotmail.com 
Dr Nazir Khan  Sher-I-Kashmir Institute of Medical Sciences  Department of Radiation oncology, ground floor, Room No 230, Soura, Srinagar, Jammu & Kashmir 190011, India Srinagar JAMMU & KASHMIR
Srinagar
JAMMU & KASHMIR 		 9419080770

drnazirkhan@rediffmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 6  
Name of Committee  Approval Status 
Ethics Committee NSCBC Research Institute  Approved 
Ethics Committee of BMCRI  Approved 
IEC-Saveetha Medical College Hospital  Approved 
Institutional Ethics Committee, Apex Hospital  Approved 
Institutional Ethics Committee, Omega Hospitals  Approved 
Institutional Ethics Committee, SKIMS Soura  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C444||Other and unspecified malignant neoplasm of skin of scalp and neck,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Parenteral TK-90  A) First Dose: (via Infusion) Prior to each radiation treatment. B) Second Dose: (via Infusion) 6 Hours after end of first infusion of the day (Hour 7) Day 1 to day 5 of every Week up to week 7. 
Comparator Agent  TK-90 Placebo  A) First Dose: (via Infusion) Prior to each radiation treatment. B) Second Dose: (via Infusion) 6 Hours after end of first infusion of the day (Hour 7) Day 1 to day 5 of every Week up to week 7. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  Participants must meet all of the following criteria at the time of screening unless otherwise specified:
1. Patient must sign study specific informed consent prior to study entry.
2. Male or Female patient aged 18 – 75 years.
3. Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx.
4. Patients must have at least 1 mucosal site of the oral cavity/oropharynx/hypopharnyx mucosa assessable by visual transoral inspection that will receive cumulative radiation dose of 70 Gy.
Note: Unavoidable doses of at least 60 Gy, to include entrance, exit, and scatter doses, still constitutes planned radiation.
5. Patients with tumors of the larynx or hypopharynx are eligible only if it is anticipated that at least 1 index site in the oral cavity/oropharynx/hypopharnyx mucosa will receive cumulative radiation dose of 70 Gy.
6. Selected Stage I to III or IVA B per AJCC, Cancer Imaging Manual, 8th edition, at study entry, including no distant metastases other than non metastatic SCCHN, based upon the following minimum diagnostic workup:
i) History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to randomization.
ii) Chest CT scan within 8 weeks prior to randomization.
iii) MRI or CT scan with contrast of tumor site within 8 weeks prior to randomization
7. Mucositis Grade less than or equal to 1 per WHO Scale and Xerostomia of Grade less than or equal to 2 per CTCAE version 5.0
8. ECOG Performance Status less than or equal to 2.
9. Adequate bone marrow function as per CTCAE V5, defined as follows (within 2 weeks prior to randomization):
i) Absolute neutrophil count more than or equal to 1500cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
ii) Platelets more than or equal to 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
iii) Hemoglobin more than or equal to 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to randomization (Note: The use of transfusion or other intervention to achieve Hgb more than 8.0 g/dl is acceptable).
10. Adequate hepatic function with bilirubin less than or equal to 1.5 x upper-normal limit (ULN), AST or ALT less than or equal 3 x ULN within 2 weeks prior to randomization.
11. Adequate renal function with serum creatinine less than 1.5 mg/dl and creatinine clearance (CrC) more than or equal 50 ml/min determined by 24 hour collection or estimated by Cockcroft Gault formula. CrC male is equal to [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]. CrC female is equal to 0.85 x (CrCl male) within 2 weeks prior to randomization.
12. Normal serum calcium or normal corrected serum calcium within 2 weeks prior to randomization formula for corrected calcium if albumin valued is below normal range Corrected calcium (mg/dl) is equal to (4 Patients albumin (g/dl) x 0.8) plus Patients measured calcium (mg/dl).
13. Negative serum pregnancy test for women of childbearing potential.
14. Women of childbearing potential and male participants with female partners of childbearing potential must practice adequate contraception.
 
 
ExclusionCriteria 
Details  Patients who meet any of the following criteria at the time of screening will be excluded:
1. Stage IVC (Any T, Any N, M1) per AJCC Cancer Staging Manual. 8th ed, or distant metastases at protocol study entry other than metastatic SCCHN.
2. Prior invasive malignancy (except non melanomatous skin cancer) unless disease free for a minimum of 3 years.
3. Patients who have not fully recovered after prior surgery. (Patients who have had prior surgery and have fully recovered and patients who may have surgery in the future are eligible.).
4. Severe, active co-morbidity, defined as follows:
i) Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV.
ii) Transmural myocardial infarction within the last 6 months.
iii) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
iv) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
v) Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
vi) Patients known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV).
5. Collagen vascular disease, such as scleroderma.
6. Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within 28 days of randomization.
7. Any prohibited therapy 2 weeks prior to randomization.
8. Pregnancy, breast feeding or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
9. Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results.
10. Known hypersensitivity study medication or excipients in the formulation.
11. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
Primary efficacy outcome measures will be SOM (Comparison of incidences of Grade 3 or 4 WHO mucositis scale in the treatment and placebo groups), and duration of SOM (Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale during the 7-week treatment period from the start of treatment. Duration is calculated from the day when an oral mucositis score of Grade 2 is reported to onset of a Grade 3 or 4 oral mucositis. Patients with a final grade 0-2 mucositis have a duration of 0).  Week 1 to Week 7 
 
Secondary Outcome  
Outcome  TimePoints 
Secondary efficacy/outcome measures will be mucositis status in the patients evaluated using two different published and validated mucositis scales: NCI/CTCAE/mucositis, and PROMS. Also, comparison of WHO scale values of treated at each point of evaluation.
Plasma concentrations of surrogate markers of mucositis, e.g., citrulline, CD40/CD40L, IL-1β, etc.
 		 Day 05 at every week upto 07 weeks and week 09 
 
Target Sample Size   Total Sample Size="24"
Sample Size from India="24" 
Final Enrollment numbers achieved (Total)= "24"
Final Enrollment numbers achieved (India)="24" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   24/06/2022 
Date of Study Completion (India) 23/02/2023 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary  

All SCCHN patients receive radiation for their disease and most of these suffer mucositis. Only palliative and ineffective treatments like ice chips, sodium bicarbonate chlorhexidine gluconate are available currently to mitigate the condition.

TK-90 for parenteral use, is a novel, non-toxic and specific therapy to prevent and treat mucositis, a major side effect of radiation treatment.

This study is designed primarily to establish, in a placebo- controlled trial, pilot efficacy compared to placebo, and secondarily to confirm the safety and tolerability of TK-90 when administered weekly for 7 weeks to patients with non-metastatic SCCHN. Success will justify exploration of use of TK-90 with other cytotoxics besides MTX and radiation therapy as well other treatments that are known to cause mucositis.

The protocol is designed to explore the anti-mucositis efficacy, tolerability, and safety of TK-90 administered daily along with their radiation treatment as an intravenous infusion in patients with non- metastatic SCCHN. The study will be partially blinded and multicenter. Relevant mucositis, tolerability, and safety endpoints will be collected in the study. Half of the patients will be given 45 mg/kg TK-90 and half will be given TK-90 placebo. All patients will be radiated. Patients at least 18-75 years old, diagnosed with non-metastatic SCCHN and scheduled to receive continuous course of radiation (e.g: 2DRT, 3DRT, IMRT etc.) as single daily fractions of 2.0 Gy, with a cumulative radiation dose of 70 Gy. The diagnosis must be confirmed by histopathology or cytology. 

Study treatments: a) Patients will be treated for 5 consecutive days with a 2 Gy radiation treatment followed by a two-day treatment holiday. b) Prior to each radiation treatment the patients will a one-hour infusion of TK-90 (45 mg/kg) or equivalent TK-90 placebo. c) 6 Hours after the end 0f the TK-90 or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment. 4) This treatment cycle will continue for 7 weeks. 5) The day before the first treatment, the patients will receive a TK-90 or TK-90 placebo administered 18 and 12 hours before the scheduled radiation treatment. 

Follow-up will occur after2 weeks of completion of last dose of radiation or early termination through up to 4 weeks.. Standard safety and anti-mucositis evaluations will occur weekly during treatment.


 
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