Phase 2a Study to Evaluate Suppression of 5-Fluorouracil -Induced Mucositis by TK112690

NCT05669521 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CLP-2690-0007
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

Patients expected to receive a 500 mg/m2 of Leucovorin by iv \& 500 mg/m2 of Fluorouracil (5FU) by iv bolus for their Colorectal Cancer. The patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization at 5 hours \& 11 hours post 5-FU iv bolus. This treatment cycle will continue weekly for 6 weeks. The TK112690 dose will be 45 mg/kg.

Conditions

Mucositis

Keywords

Mucositis; Uridine Phosphorylase Inhibitor; Chemotherapy; 5 FU/ LU; Colorectal cancer

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. 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. Subjects 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

  8 Weeks

Secondary Outcomes (1)

• Secondary efficacy/outcome mucositis

  8 Weeks

Study Arms (2)

TK112690

EXPERIMENTAL

TK112690 treatment

Drug: TK-112690

Placebo

PLACEBO COMPARATOR

TK112690 formulation

Drug: Placebo

Interventions

TK-112690 DRUG

TK112690 treatment Post 5-FU chemotherapy

TK112690

Placebo DRUG

Placebo treatment Post 5-FU chemotherapy

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:

• Male and female patients 18 to 75 years old (both inclusive) with a histologically or cytological confirmed diagnosis of colorectal cancer
• 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.
• No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.
• Be able to read and understand and provide a signature or thumb impression on the Informed Consent Form (ICF) before entering the study.
• No other concurrent, active, invasive malignancy.
• ECOG performance status of 0 to 2.
• Must have a life expectancy of at least 6 months.
• No active angina or uncontrolled arrhythmia.
• 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.
• Mucositis Grade less than or equal to 1 per WHO Scale and Xerostomia of Grade less than or equal to 2 per CTCAE
• 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).
• 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 3x ULN within 2 weeks prior to randomization
• 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)
• 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).

You may not qualify if:

• An active infection including HIV/ HBV/ HCV infection.
• 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.)
• Unstabilized or symptomatic brain metastasis (History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy).
• Pregnant or nursing mother.
• Prior history of a cerebrovascular accident or hemorrhage.
• Congestive heart failure, as defined by New York Heart Association class III or IV.
• Uncontrolled hypertension.
• Active psychiatric/mental illness making informed consent or useful clinical follow-up unlikely.
• Patients who have previously been enrolled into this study and subsequently withdrew.
• Patient receiving other investigational agent(s).
• Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).
• Any prohibited prior or concomitant therapy 2 weeks prior to enrollment.
• 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.
• Known or suspected intolerance or hypersensitivity to the study materials (TK 90 and/or excipients or closely related compounds).
• Patients that have a history of poor compliance in clinical research studies.

Sponsors & Collaborators

• Tosk, Inc.: lead
• SIRO Clinpharm Pvt. Ltd.: collaborator

Study Sites (5)

Jawaharlal Nehru Cancer Hospital and Research Centre

Bhopal, Madhya Pradesh, 462001, India

Location

Om Sai Onco Surgery Multispecialty Hospital Center

Kolhāpur, Maharashtra, 416006, India

Location

B. J. Medical College and Sassoon General Hospital

Pune, Maharashtra, 411001, India

Location

MTES Sanjeevan Hospital

Pune, Maharashtra, 411001, India

Location

Saveetha Medical college Chennai

Chennai, Tamil Nadu, 602105, India

Location

MeSH Terms

Conditions

Mucositis; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

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 5, 2022
• First Posted: January 3, 2023
• Study Start: June 15, 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)