Phase 2a Study to Evaluate Suppression of Radiotherapy-induced Mucositis by TK112690

NCT05658016 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CLP-2690-0004
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

Patients expected to receive a continuous course of radiation as single daily fractions of 2.0 Gy treatment with a cumulative radiation dose of 70 Gy. The radiation can be 2DRT, 3DRT,IMRT etc. Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization. 6 Hours after the completion of TK-90 infusion or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment depending on randomization. This treatment cycle will continue for 7 weeks. The TK112690 dose will be 45 mg/kg.

Conditions

Mucositis

Keywords

Mucositis; Uridine Phosphorylase Inhibitor; Head and Neck Cancer; Radiation

Outcome Measures

Primary Outcomes (1)

• Mucositis

  * SOM (Severe Oral Mucositis) - Comparison of incidences of Grade 3 or 4 mucositis (WHO scale) in the treatment and placebo groups. * Duration of SOM (Severe Oral Mucositis). Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale from the start of treatment. * Calculate Number of days from the first occurrence of WHO Grade 3 or 4 oral mucositis through the first occurrence of non-severe (≤ Grade 2) without a subsequent instance of ≥ Grade 3 oral mucositis. * Subjects with complete study follow-up for SOM who do not develop severe oral mucositis (grade 0-2) will be considered to have duration of 0 days.

  7 weeks

Secondary Outcomes (2)

• Secondary efficacy/outcome mucositis

  7 weeks

• Incidence Adverse Events That Are Related to Treatment

  7 Weeks

Study Arms (2)

TK112690

EXPERIMENTAL

TK112690 treatment

Drug: TK-112690

Placebo

PLACEBO COMPARATOR

TK112690 formulation

Drug: Placebo

Interventions

TK-112690 DRUG

TK112690 treatment Pre \& Post Radiation

TK112690

Placebo DRUG

TK112690 Placebo treatment Pre \& Post Radiation

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet ALL of the following criteria at the time of screening unless otherwise specified:
• Patient must sign study specific informed consent prior to study entry.
• Male or Female patient aged 18 - 75 years.
• 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.
• Patients must have at least 1 mucosal site of the oral cavity/oropharynx/hypopharynx 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.
• 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/hypopharynx mucosa (Refer section 10.13.1) will receive cumulative radiation dose of 70 Gy.
• 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:
• History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to randomization.
• Chest CT scan within 8 weeks prior to randomization.
• MRI or CT scan with contrast of tumor site within 8 weeks prior to randomization.
• Mucositis Grade ≤ 1 per WHO Scale and Xerostomia of Grade ≤ 2 per CTCAE version 5.0
• ECOG Performance Status ≤ 2.
• Adequate bone marrow function as per CTCAE V 5, defined as follows (within 2 weeks prior to randomization):
• Absolute neutrophil count ≥ 1500cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.

You may not qualify if:

• Patients who meet any of the following criteria at the time of screening will be excluded:
• 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.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
• 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.).
• 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).
• Collagen vascular disease, such as scleroderma.
• Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within 28 days of randomization.
• Any prohibited therapy 2 weeks prior to randomization (see Section 8.4).
• 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.

Sponsors & Collaborators

• Tosk, Inc.: lead
• SIRO Clinpharm Private Limited: collaborator

Study Sites (5)

Sher-I-Kashmir Institute of Medical Sciences

Srinagar, Jammu and Kashmir, 190011, India

Location

Bangalore Medical college and Research Institute

Bangalore, Karnataka, 560002, India

Location

Saveetha Medical College and Hospita

Chennai, Tamil Nadu, 602105, India

Location

Apex Hospital

Varanasi, Uttar Pradesh, 221004, India

Location

Netaji Subhash Chandra Bose Hospital

Kolkata, West Bengal, 700094, India

Location

MeSH Terms

Conditions

Mucositis; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms

Study Officials

• Emile Youssef, MD, PhD

  Tosk, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study will be partially blinded. The patient and investigator as well as site personnel will be blinded as to whether TK-90 or TK-90 placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or TK-90 placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A total of 24 patients will be enrolled into one of 2 different: TK112690 treated or placebo treated.

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 20, 2022
• Study Start: June 17, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

IN (5)