CTRI/2023/11/060212 [Registered on: 23/11/2023] Trial Registered Prospectively
Last Modified On:
12/11/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A clinical trial to study the Dose, Safety and tolerance of TK-112690 injection in Head and Neck cancer patients receiving radiation and chemotherapy
Scientific Title of Study
A Phase 2a, Multi-center, Open Label, Dose Optimization, Pilot Study to Assess the Safety and Tolerability at the Maximum Tolerated Dose of Parenteral TK-112690 in Non-Metastatic Squamous Cell Carcinoma of Head and Neck Patients Scheduled to Receive Chemoradiation.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CLP-2690-0008 Version 1.0 dated 01-Jul-2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sagar Bhosale
Designation
Managing Director Tosk Inc. India
Affiliation
Tosk Inc
Address
Tosk, Inc. 179/176 (I), Alto Bella Vista, Sangolda, Porvorim, Goa,
India - 403521
North Goa GOA 403521 India
Phone
7989955147
Fax
Email
sbhosale@tosk.com
Details of Contact Person Scientific Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt.Ltd
Address
Office No. 02, 03 & 04, Second Floor,
Highland Corporate Center,
Kapurbawdi Junction, Thane (W) 400 607,
Maharashtra, India
Thane MAHARASHTRA 400607 India
Phone
02241006794
Fax
Email
drneeta@biospherecro.com
Details of Contact Person Public Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt.Ltd
Address
Office No. 02, 03 & 04, Second Floor,
Highland Corporate Center,
Kapurbawdi Junction, Thane (W) 400 607,
Maharashtra, India
MAHARASHTRA 400607 India
Phone
02241006794
Fax
Email
drneeta@biospherecro.com
Source of Monetary or Material Support
Tosk Inc,2672 Bayshore Parkway, Suite 507
Mountain View, CA 94043 USA
Primary Sponsor
Name
Tosk Inc
Address
2672 Bayshore Parkway, Suite 507 Mountain View, CA 94043 USA
Department of clinical research, ground floor,shree Narsimha saraswati medical foundation, Alandi-Chakan Road, Alandi-Devachi, Pune, Maharashtra-412105, India. Pune MAHARASHTRA
9967835653
drbhooshan@gmail.com
Dr Yathish Kumar HM
Karnataka Cancer Hospital
Ground Floor, 99,Kanteerava Studio Main Rd, Krishnananda Nagar, Yeshanthpur,Bengaluru - 560096, Karnataka, India. Bangalore KARNATAKA
9880462912
dryathish@hotmail.com
DrSatish Sonawane
Maccare Superspeciality Hospital Ahmednagar
Clinical Research Department,4th Floor, Behind Zopadi Canteen, Opp St Monica D.ed College, Savedi, Ahmednagar, 414003. Ahmadnagar MAHARASHTRA
Narsimha Saraswati Medical Foundation Ethics Committee, Indrayani Hospital and Cancer Institute
Submittted/Under Review
Om Sai Onco Institutional Ethics Committee
Approved
Pranav Diabetes Center Ethics Committee, Bangalore
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
Placebo Injection
Placebo vials identical to TK-90 dose. It will be compared with the maximum tolerated dose assessed in the study for pharmacokinetic assessment.
Intervention
TK-112690 injection
TK-90 injection will be administered around 60 mins infusion within 1-hour prior to radiation on Days 1-5 for Weeks 6-7 weeks.
The ascending doses to be studied are 75mg/kg, 90mg/kg, 105mg/kg and 120 mg/kg
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Patient must sign study-specific Informed consent prior to study entry.
2. Male or Female patients 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 (Refer Definition in 10.13.1), 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 60-70 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 (Refer section 10.13.1) will receive cumulative radiation dose of 60-70 Gy.
6. Patients with Stage I to III or IVA-B as 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:
- History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to enrollment.
- PET /CT Scan/MRI within 8 weeks of enrollment.
7. Mucositis Grade ≤ 1 per WHO Scale and Xerostomia of Grade ≤ 2 per CTCAE version 5.0.
8. ECOG Performance Status ≤ 2.
9. Adequate bone marrow function as per CTCAE V 5, defined as follows (within 2 weeks prior to enrollment):
- Absolute neutrophil count ≥ 1500 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to enrollment.
- Platelets ≥ 100,000 cells/mm3 based upon CBC obtained within 2 weeks prior to enrollment.
- Hemoglobin ≥ 8.0 g/dl based upon CBC obtained within 2 weeks prior to randomization (Note: The use of transfusion or other intervention to achieve Hgb> 8.0 g/dl is acceptable).
10. Adequate hepatic function with bilirubin ≤ 1.5 x upper-normal limit (ULN), AST or ALT
≤3 x ULN within 2 weeks prior to enrollment.
11. Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance (CrC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula. CrC male equals [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]. CrC female equals 0.85 x (CrCl male) within 2 weeks prior to enrollment.
12. Negative serum pregnancy test for women of childbearing potential.
13. Women of childbearing potential and male participants with female partners of childbearing potential must practice adequate contraception.
ExclusionCriteria
Details
1. Stage IVC (Any T, Any N, M1) per AJCC Cancer Staging Manual. 8th ed, or distant metastases at protocol study entry.
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 to SCCHN surgery. (Except those 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:
-Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV.
-Transmural myocardial infarction within the last 6 months.
-Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
-Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
-Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
-Patients known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV).
5. Concurrent available or experimental systemic or topical pharmaceuticals or devices or low-level laser therapy for OM. Oral rinses—limited to sodium bicarbonate, lidocaine, and antifungal agents—will be permitted. Supportive care per ASCO guidelines is permitted and encouraged.
6. Collagen vascular disease, such as scleroderma.
7. Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within a month of enrollment.
8. Any prohibited therapy 2 weeks prior to enrollment. (see Section 8.4)
9. Pregnancy, breast feeding or women of childbearing potential and men who a sexually active and not willing/able to use medically acceptable forms of contraception.
10. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
11. Known hypersensitivity study medication or excipients in the formulation.
12. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
13. The use of steroids during treatment.
14. Supportive care is allowed after approval of medical monitoring
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
1.DLTs- Any grade ≥3 DLTs during study graded according to the CTCAE, v5.0 that cannot clearly be attributed to a cause other than TK-112690.
2.MTD. Highest dose administered that is not associated with a DLT if three patients are treated or two or more DLTs if 6 patients are treated.
3.RP3D. Dose based on achieving a MTD or achieving a plasma concentration expected to be efficacious based on animal experiments with TK-112690.
4.Incidence of radiation induced mucositis (RIM).
7 weeks
Secondary Outcome
Outcome
TimePoints
NIL
NIL
Target Sample Size
Total Sample Size="30" Sample Size from India="30" 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
This is a multi-center, open label, dose optimization, pilot study to assess the safety, and tolerability at the maximum tolerated dose of Parenteral TK-112690 in non-metastatic squamous cell carcinoma of head and neck patients scheduled to receive chemoradiation.
A classic “3+3†design will be used to establish dose limiting toxicities (DLT), maximum tolerated dose (MTD). Three to six patients per treatment cohort will be assigned to receive sequentially escalating dose tiers of parenterally administered TK-112690 once for Day 1 to 5 (a “Cycleâ€), starting at a dose of 75mg/kg dose.
Cohort of three patients will be enrolled sequentially into escalating dose tiers of TK-90. Dose escalation will be conducted for each treatment group following a 3+3-design where cohorts of three patients will be treated per dose until the MTD is found at which no patient more than one out of three patients experience a DLT in the treatment course cohort. If one patients in a cohort experience a DLTs, another three patients will be enrolled in the same cohort; thus the DLT is defined as one patient out of three or two patients out of six patients . The starting dose for testing will be 75mg/kg. If there are no DLTs as defined above in the dose cohort, then the dose would be escalated by 15 mg/kg for 2nd, 3rd & 4th cohort. The maximum proposed TK-112690 dose is 120 mg/kg,.
- Expected ascending doses are 75, 90, 105 and 120 mg/kg.
- If DLT is observed at 75mg/kg cohort, the dose will be de-escalated to 60 mg/kg or 45 mg/kg in new patients following the same study design.
- Patients will remain for observation and PK sampling at the clinical site for a minimum of 8 hours post initial TK-112690 on Day 1 & Day 5 of Week 1
- If the TK-112690 is well tolerated and there are no safety concerns by end of Day 21(out of the 6 or 7 weeks cycle) post initial infusion, the second dose cohort will be initiated simultaneously. The treatment period for the study is 6-7 weeks.
Screening must be completed within 21 days of patient enrollment.
-Study follow-up will be scheduled post two weeks of completion of last dose of radiation or early termination through up to 4 weeks. If a patient has ulcerative SOM (WHO ≥ 3) at the last day of radiation therapy, visits for SOM will be repeated biweekly (at least 72 hrs apart) until the WHO score is 0 or 1 or the patient is 4 week’s post-radiation therapy, whichever occurs first.
-Weekly radiation treatments
o Patients will be treated for 5 consecutive days with a 2 Gy radiation treatment followed by a two-day treatment holiday.
o Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 (75 mg/kg) for Cohort 1 which will be escalated by 15 mg/kg for 2nd, 3rd & 4th cohort. the maximum proposed TK-112690 dose is 120 mg/kg
o At Day 3 of every radiation cycle, cisplatin as chemotherapy should be administered intravenously at a dose of 40 mg/m2. Cisplatin should be administered intravenously followed by the study medication administration and radiotherapy within 1 hour of the study medication administration, with pre-medications and adequate hydration protocol.
o This treatment cycle will continue for 6 -7 weeks.
o The final follow up will be conducted at Visit 10 (Week 9)
- Patients will receive TK-90 before 1 hour of the scheduled initiation radiation treatment.
- Standard safety evaluations will occur weekly during treatment.
- Mucositis assessment will be performed 2 times a week, i.e. Day 1 and Day 5 by PI, CO-Investigators, etc.
- PK sampling: At Treatment Week 1, Day1, blood samples will be collected pre-dose and then at 1, 2, 4, 6, and 8 hour’s post-dose after the administration of the first dose of the first cycle. At Day 2, Day 3, Day 4 blood samples will be collected prior to dosing and 1hr after dosing. At Day 5 blood samples will be collected pre-dose and then at 1, 2, 4, 6, and 8 hour’s post-dose after the administration. At Day 8 pre-dose sample will be collected