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

Phase 2

Completed

Brief Summary: Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion along with a nutritional supplement administered two hours before the methotrexate. One hour before the methotrexate treatment the patients will be administered the first infusion of the day of either TK112690 or placebo depending on randomization. Five hours after the methotrexate treatment the patients will be administered the second treatment of either TK112690 or placebo depending on randomization. The TK112690 dose will be 45 mg/kg.

Detailed Description: Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion along with a nutritional supplement administered two hours before the methotrexate. One hour before the methotrexate treatment the patients will be administered the first infusion of the day of either TK112690 or placebo depending on randomization infusion. Five hours after the methotrexate treatment the patients will be administered the second treatment of either TK112690 or placebo depending on randomization. The TK112690 dose will be 45 mg/kg.

* A total of 22 patients will be enrolled into one of 2 different dose groups: TK-112690 treated or placebo treated.

* Screening must be within 15 days of subject enrollment.

* Patients will remain for observation at the clinical site for a minimum of 25 hours post initial TK112690 or placebo dose.

* Study follow-up will occur on Week 6, two weeks after the last dosing of methotrexate.

* Blinding: The study will be partially blinded. The patient and investigator will be blinded as to whether TK112690 or placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or placebo.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Subject has not failed at least one courses of non-MTX chemotherapy or one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN.
Uncontrolled active infection.
Current mucositis (>Grade 1).
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.
Subjects who have previously been enrolled into this study and subsequently withdrew.
Subject receiving other investigational agent(s).
Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).
Any significant systemic illness, unstable or severe medical condition(s) that could put the subject 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-112690 and/or excipients or closely related compounds).
Subjects, who have received, or plan to receive, radiation or chemotherapy within 4 weeks of screening.
Subjects that have a history of poor compliance in clinical research studies.
Subjects that have participated in any other investigative clinical trial in the past 4 weeks.

Arm && Interventions

Group	Intervention	Description
TK112690	TK-112690	TK112690 treatment
Placebo	Placebo TK-112690	TK112690 formulation

Primary Outcome Measures

Name	Time	Method
Mucositis	up to 4 Weeks	Mucositis Evaluation Using Established Scoring Systems: NCI/CTCAE at 4 WKs (Primary) and WHO at 4 WKs (Primary). NCI/CTCAE=National Cancer Institute/Common Terminology Criteria for Adverse Events and WHO=World Health Organization NCI Grades- 0= No mucositis, 1=Mild mucositis (Painless ulcers, erythema, or mild soreness in the absence of lesions), 2=Moderate mucositis (Painful erythema, edema, or ulcers but eating or swallowing possible), 3= Severe mucositis (Painful erythema, edema, or ulcers requiring IV hydration), 4=Life threatening, 5=Death WHO Grades- 0=No mucositis, 1= Mild (Oral soreness, erythema), 2=Moderate (Oral erythema, ulcers, solid diet tolerated), 3=Severe (Oral ulcers, liquid diet only), 4=Life-threatening (Oral alimentation impossible). For both the scales above, a higher score implies greater mucositis. Scale specific mean values for patients in each group (placebo or treated) are calculated and compared by Student's t-test.

Secondary Outcome Measures

Name	Time	Method
Incidence Adverse Events That Are Related to Treatment	Measured Weekly Over 4 Weeks of Study	Tolerance

Locations (3): Bangalore Cancer
🇮🇳
Bangalore, Karnataka, India
Karnatak Cancer Therapy and Research Institute
🇮🇳
Navanagar, Karnataka, India
Netaji Subhash Chandra Bose Cancer Hospital
🇮🇳
Kolkata, West Bengal, India