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CTRI Number  CTRI/2022/06/043202 [Registered on: 13/06/2022] Trial Registered Prospectively
Last Modified On: 10/04/2024
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 clinical study to access safety and efficacy of TK-90 or parenteral TK-90 placebo in patients with colorectal cancer scheduled to receive bolus 5-fluorouracil and infused leucovorin. 
Scientific Title of Study   A Phase 2a, multi-center, placebo-controlled, randomized, assessor blind study of bolus 5-fluorouracil and infused leucovorin plus either infused TK 90 for parenteral use or infused TK 90 placebo administered weekly for 6 consecutive weeks to patients with colorectal cancer.  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CLP-2690-0007 Protocol Version 2.0 Dated 21-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

North Goa
GOA
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 and 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) - 400604, Maharashtra, India.

Thane
MAHARASHTRA
400604
India 
Phone  022-6108-8000   
Fax  022-6108-8081  
Email  ganesh.divekar@siroclinpharm.com  
 
Details of Contact Person
Public Query  
Name  Dr Ganesh Divekar 
Designation  Vice President - Clinical Operations, Biometrics and 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) - 400604, Maharashtra, India.


MAHARASHTRA
400604
India 
Phone  022-6108-8000   
Fax  022-6108-8081  
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 = 7  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Kiran Kumar Jadhav   B. J. Medical College and Sassoon General Hospital   1st floor, Department of Surgery, B. J. Medical College and Sassoon General Hospital, Sassoon Road, Somwar Peth, Pune - 411001, Maharashtra, India
Pune
MAHARASHTRA 		 02026128000

drj.kirankumar@gmail.com 
Dr Minish Jain   Grant Medical Foundation Ruby Hall Clinic  Department of medical Oncology 40, Sassoon Road, Pune 411001
Pune
MAHARASHTRA 		 9823133390

minishjain009@gmail.com 
Dr Srikant Tiwari  Jawaharlal Nehru Cancer Hospital and Research Centre  P.B, No. 32, Cancer Hospital Rd, Idgah Hills, Bhopal, Madhya Pradesh - 462001
Bhopal
MADHYA PRADESH 		 9958783620

srikantabhinov@gmail.com 
Dr Bahar Kulkarni  MTES Sanjeevan Hospital  Department of medical Oncology Plot No. 23, off karve road Erandwane, Pune 411004
Pune
MAHARASHTRA 		 020-67250000

Drbahar.kulkarni96@gmail.com 
Dr Prashant Lad  Om Sai Onco Surgery Multispecialty Hospital Center  R. S. No. 457/10, Dr. LAD Colony, Sugar Mill Corner,, Main Road, Kasaba Bawada, Kolhapur, Maharashtra 416006
Kolhapur
MAHARASHTRA 		 8237772626

omsaicr17@gmail.com 
Dr Anita Ramesh  Saveetha Medical college Chennai  Saveetha Nagar, Thandalam, Chennai Bengaluru NH 48, Chennai, Tamil Nadu 602105
Chennai
TAMIL NADU 		 9840758567

anitachandra100@hotmail.com 
Dr Deepak Kumar Singh  Swami Harshankaranand Ji Hospital And Research Center  N8/237, BHU Road, Near Bhikaripur crossing, Opp Union Bank of India, B.H.U, Sundarpur Newada, Varanasi, Uttar Pradesh - 221005
Varanasi
UTTAR PRADESH 		 9450428608

deepakbhu@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 7  
Name of Committee  Approval Status 
Ethics Committee Sanjevan Hospital  Approved 
Institutional Ethics Committee B.J. Medical college and Sassoon General Hospital  Approved 
Institutional Ethics Committee Saveetha Medical College and Hospital  Approved 
Institutional Ethics Committee, Jawaharlal Nehru cancer hospital and research centre  Approved 
Institutional Ethics Committee, Shubham Sudbhawana Super Speciality Hospital  Approved 
Om Sai Onco Institutional Ethics Committee  Approved 
Poona Medical Research Foundation, Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C189||Malignant neoplasm of colon, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Parenteral TK-90  Administered as an infusion A) Background Medication: i) LV: (Hour-0) Dose of 500 mg/m2 Intravenous infusion over two hours (window period ± 30 mins). ii) 5-FU: (Hour-1) Dose of 500 mg/m2 Intravenous bolus (window period ± 10 mins). B) TK-90 Infusion: i) First Dose: (Hour-5) Dose of 45mg/kg IV over one hour (window period ± 15 mins). ii) Second Dose: (Hour-11) Dose of 45mg/kg IV over one hour (window period ± 15 mins).  
Comparator Agent  Parenteral TK-90 Placebo  Administered as an infusion A) Background Medication: i) LV: (Hour-0) Dose of 500 mg/m2 Intravenous infusion over two hours (window period ± 30 mins). ii) 5-FU: (Hour-1) Dose of 500 mg/m2 Intravenous bolus (window period ± 10 mins). B) TK-90 Placebo Infusion: i) First Dose: (Hour-5) Dose of 45mg/kg IV over one hour (window period ± 15 mins). ii) Second Dose: (Hour-11) Dose of 45mg/kg IV over one hour (window period ± 15 mins). 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1. Male and female patients 18 to 75 years old (both inclusive) with a histologically or cytological confirmed diagnosis of colorectal cancer
2. Patient scheduled to receive bolus 5 FU along with LV as first line or subsequent therapy for treating locally advanced or residual or recurrent or metastatic colorectal cancer.
3. No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.
4. Be able to read and understand and provide a signature or thumb impression on the Informed
Consent Form (ICF) before entering the study.
5. No other concurrent, active, invasive malignancy.
6. ECOG performance status of 0 to 2.
7. Must have a life expectancy of at least 6 months.
8. No active angina or uncontrolled arrhythmia.
9. Not pregnant or nursing. Women of childbearing potential must have a negative serum
pregnancy test at screening and on the day before dosing and must use medically acceptable
methods of birth control. Acceptable methods of birth control include oral or transdermal
contraceptives, condoms, spermicidal foam, IUD, progestin implant or injection, abstinence,
vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as
bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or post-menopausal for more than or equal to 1 year, must be specified in the patient’s medical history file and CRF.
10. Mucositis Grade less than or equal to 1 per WHO Scale and Xerostomia of Grade less than or equal to 2 per CTCAE
11. Adequate bone marrow function as per CTCAE V5, defined as follows:
i) Absolute neutrophil count more than or equal to 1500 cells/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).
12. Adequate hepatic function with bilirubin less than or equal to 1.5 x upper-normal limit (ULN), AST or ALT less than or equal to 3
x ULN within 2 weeks prior to randomization
13. Adequate renal function with serum creatinine less than 1.5 mg/dl and creatinine clearance (CrC) more than or equal to 50 ml/min within 2 weeks prior to randomization 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)
14. 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) + patient measured calcium (mg/dl).


 
 
ExclusionCriteria 
Details  1. An active infection including HIV/ HBV/ HCV infection.
2. 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.)
3. Unstabilized or symptomatic brain metastasis (History of brain metastases allowed if disease
has stabilized or improved after radiation and/or craniotomy).
4. Pregnant or nursing mother.
5. Prior history of a cerebrovascular accident or hemorrhage.
6. Congestive heart failure, as defined by New York Heart Association class III or IV.
7. Uncontrolled hypertension.
8. Active psychiatric/mental illness making informed consent or useful clinical follow-up
unlikely.
9. Patients who have previously been enrolled into this study and subsequently withdrew.
10. Patient receiving other investigational agent(s).
11. Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).
12. Any prohibited prior or concomitant therapy 2 weeks prior to enrollment.
13. Presence of any significant systemic illness, unstable or severe medical condition(s) that could
put the patient at risk during the study, interfere with outcome measures, or affect compliance
with the protocol procedures such as intercurrent infection and/or autoimmune disease, ie, any
condition that compromises the immune system.
14. Known or suspected intolerance or hypersensitivity to the study materials (TK 90 and/or excipients or closely related compounds).
15. Patients that have a history of poor compliance in clinical research studies.
16. Patients that have participated in any other investigative clinical trial in the past 4 weeks.

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
A) SOM (Severe Oral Mucositis) - Comparison of incidences of Grade 3 or 4 mucositis (WHO scale) in the treatment (TK-90) and TK-90 placebo groups. B) Duration of SOM - Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale from the start of treatment; number of days from the first occurrence of WHO Grade 3 or 4 OM through the first occurrence of non-severe (≤ Grade 2) without a subsequent instance of ≥ Grade 3 OM. patients with complete study follow-up for severe OM who do not develop severe OM (grade 0-2) will be considered to have durations of 0 days.  48 Hr and 96 hr every week upto week 06 and at week 08 
 
Secondary Outcome  
Outcome  TimePoints 
A) In addition to the WHO scale, mucositis status in the patients will also be evaluated using two different published and validated mucositis scales: NCI/CTCAE/mucositis, and PROMS.
B) Comparison of WHO scale values of treated patients at each point of evaluation. 		 48 Hr and 96 hr every week upto week 06 and at week 08 
 
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)
Modification(s)  		 26/07/2022 
Date of Study Completion (India) 07/06/2023 
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  

5-FU, a structural analogue of uracil, is used as a chemotherapeutic agent for various malignancies including CRC. One of the major toxic effects of 5-FU is intestinal injury, apparently mediated by both the direct effect of 5-FU, and an indirect effect produced by infiltration of gut bacteria and gut bacteria-associated toxins into systemic circulation through the impaired mucosal barrier.

TK-90 for parenteral use, is a novel, non-toxic and specific therapy to prevent and treat mucositis, a major side effect of 5-FU.

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 6 weeks along with 5-FU/LV to patients with local, advanced, recurrent, metastatic CRC. Success will justify exploration of use of TK-90 with other cytotoxics besides MTX and 5-FU, radiation therapy, and other treatments that are known to cause mucositis.

 
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