A Phase 1b, Multi-center, Study of New Drug METREXASSISTTM (Parenteral TK-112690) given with Methotrexate as a Weekly Infusion to Subjects with Head and Neck cancer patients Undergoing Treatment with Methotrexate. A Dose Increasing/Safety study with No Control

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/05/008587
• Date of registration: 17-05-2017
• Prospective Registration: Yes
• Primary sponsor: Tosk Inc
• Public title: A Phase 1b, Multi-center, Study of New Drug METREXASSISTTM (Parenteral TK-112690) given with Methotrexate as a Weekly Infusion to Subjects with Head and Neck cancer patients Undergoing Treatment with Methotrexate. A Dose Increasing/Safety study with No Control
• Scientific title: A Phase 1b, Multi-center, Study of METREXASSISTTM (Parenteral TK-112690) Administered in Combination with Methotrexate as a Weekly Infusion to Subjects with SCCHN Undergoing Treatment with Methotrexate. A Dose Escalation/Safety study with No Control
• Date of first enrolment: 05-06-2017
• Target sample size: 25
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18911
• Study type: Interventional
• Study design: Non-randomized, Active Controlled Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 1

Countries of recruitment

India

Contacts

• Name: Dr L Krishna Murthy
• Affiliation: CRBio ( A Division of RA CHEM PHARMA)

• Name: Dr Sagar Bhosale
• Affiliation: CRBio ( A Division of RA CHEM PHARMA)

Key inclusion & exclusion criteria

Inclusion criteria: • Male and female subjects over 18 years old with a histologically or cytologically confirmed diagnosis of locally advanced, recurrent or metastatic SCCHN, any stage of disease.

• No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.

• No other concurrent, active, invasive malignancies.

• An Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

• Must have a life expectancy of at least 6 months.

• History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy.

• No active angina or uncontrolled arrhythmia.

• No detectable infection including hepatitis B/C and HIV.

• No other concurrent, active, invasive malignancies

• Not pregnant or nursing. Women of childbearing potential must have a negative urine 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 >= 1 year, must be specified on the patientâ??s medical history file and CRF.

• Must have adequate organ and immune function as indicated by the following laboratory values:

Parameter Laboratory Values

Serum creatinine £1.5 x ULN

Estimated creatinine clearance ³45 mL/min

Total bilirubin £2.0 mg/dL (£34.2 mmol/L)

AST & ALT £3 x ULN

Absolute granulocytes ³1.5 x 109 cells/L

Platelets ³ 100,000/µL

• Be able to read, understand, and willing to sign the Informed Consent Form (ICF) before entering the study


Exclusion criteria: • Uncontrolled active infection.

• Current mucositis ( >Grade 1).

• Pregnancy 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 another investigational agent(s).

• Any systemic immunosuppressive medication/therapy (e.g., 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, i.e., 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 who have participated in any other investigative clinical trial in the past 4 weeks



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Squamous Cell Carcinoma of Head and Neck

Intervention(s)

Intervention1: TK-112690: Dose cohorts will receive MTX at a dose of 60 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion. TK-112690 will be administered as a one-hour infusion one hour before and 5 hours after each MTX dose along with a nutritional supplement containing uridine monophosphate (Fortasyn Connectâ?¢, Nutricia NV) administered one hour before the first TK-112690 infusion of the day
Four ascending doses TK-112690 with a confirmatory repeat of the top tolerated dose
Control Intervention1: Not Applicable: Not Applicable

Primary Outcome(s)

DLTs: Any grade 3 or 4 dose-limiting systemic toxicity during the study graded according to the CTCAE (NCI Common Terminology Criteria for Adverse Events), v 4.0 that cannot clearly be attributed to a cause other than TK-112690Timepoint: 24 hrs,48 hrs of 1 to 4 week and week 5 and week 8 for Mucositiis Assessment

Secondary Outcome(s)

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.

PK. Confirmation that the PK of TK-112690 in patients is similar to the PK profile in healthy volunteers based on WinNonlin analysis of drug plasma concentrations.

Biomarker. Demonstration theTimepoint: after PK,Biomarkers and surrogate Markers assessment

Secondary ID(s)

CLP-2690-0002 Version 02 05/09/2016

Source(s) of Monetary Support

Tosk,Inc. 2672 Bayshore Parkway, Suite 507 Mountain View, CA 94043

Ethics review

Status: Approved
Approval date: 03/04/2017
Contact:

MANAS HOSPITAL ETHICS COMMITTEE

Status: Approved
Approval date: 25/06/2017
Contact:

Institutional Ethics Committee for M.V. Hospital and Research Center

Status: Approved
Approval date: 29/07/2017
Contact:

Sudbhawana Hospital Ethics Committee

Status: Approved
Approval date: 18/09/2017
Contact:

Ethics Committee Sanjeevan Hospital

Status: Approved
Approval date: 16/01/2018
Contact:

IEC of B. J. GOVT. MEDICAL COLLEGE & SASSOON GENERAL HOSPITALS

Status: Not Applicable
Approval date:
Contact:

Ethics Committee G.S.V. M. Medical College

Results

• Date Completed: 29/06/2018