| CTRI Number |
CTRI/2019/05/018909 [Registered on: 02/05/2019] Trial Registered Prospectively |
| Last Modified On: |
16/11/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A clinical trial to study the efficacy & Safety of IV of TK-112690 a new experimental drug to a placebo as a mucositis preventive in subjects with squamous cell cancer of Head & Neck scheduled to receive Methotrexate as chemotherapy |
|
Scientific Title of Study
|
A Phase 2a, Multi-center, Placebo-controlled, Randomized Partially Blinded, Study of Infused METREXASSISTâ„¢ (Parenteral TK-112690) or Metrexassistâ„¢ Placebo Administered Along with Methotrexate Weekly for Four Consecutive Weeks to Patients with Recurrent or Residual SCCHN. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CLP-2690-0003, Version 3.0, dated 06 March 2019 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Anupam Datta |
| Designation |
Principal Investigator |
| Affiliation |
Netaji Subash Chandra Bose Cancer Research Institute, |
| Address |
Netaji Subash Chandra Bose Cancer Research Institute,Department of Radiation Oncology 3081 Nayabad Ave New Garia Pancha Sayar
Kolkata
WEST BENGAL
700094
India |
| Phone |
|
| Fax |
|
| Email |
dranupamdatta@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr L Krishnamurthy |
| Designation |
Medical Monitor |
| Affiliation |
Crystal Life Sciences |
| Address |
Crystal Life Sciences
Office Number 812 8th Floor
Global Business Hub Near Eon Free Zone Kharadi
Pune
MAHARASHTRA
411014
India |
| Phone |
02029705298 |
| Fax |
|
| Email |
dr_murthy130475@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sagar Bhosale |
| Designation |
Deputy General Manager |
| Affiliation |
Crystal Life Sciences |
| Address |
Crystal Life Sciences
Office Number 812 8th Floor
Global Business Hub Near Eon Free Zone Kharadi
Pune
MAHARASHTRA
411014
India |
| Phone |
7989955147 |
| Fax |
|
| Email |
drsagar@crystallifesciences.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 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Anil Kumar MR |
Bangalore Cancer Centre |
Bangalore Cancer Centre, Department of Radiation Oncology, 118/1-2 , Machohalli forest gate, Magadi Main Rd, Bengaluru, Karnataka 560091
Bangalore
KARNATAKA |
9739808502
dranil.onco@gmail.com |
| Dr Kiran Ashok Kattimani |
Karnataka Cancer Therapy & Research Institute |
Karnataka Cancer Therapy & Research Institute, Department of Medical Oncology, Navanagar, Hubli, Karnataka 580025
Dharwad
KARNATAKA |
9480616656
dr_kattimani@yahoo.com |
| Dr Anupam Datta |
Netaji Subash Chandra Bose Cancer Research Institute |
Netaji Subash Chandra Bose Cancer Research Institute, Department of Radiation Oncology, 3081, Nayabad Ave, New Garia, Pancha Sayar, Kolkata,
Kolkata
WEST BENGAL |
9894873282
dranupamdatta@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Institutional Ethic Committee Bangalore Cancer Center |
Approved |
| Institutional Ethic Committee Karnataka Cancer Therapy & Research Institute |
Approved |
| Institutional Ethic Committee Netaji Subash Chandra Bose Cancer Research Institute |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
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 |
The Placebo is a isotonic saline in 10 mL
glass vials will be substituted for the 10 mL TK-112690 vials.
Placebo is administered weekly for 4 consecutive weeks as an iv infusion one hour before methotrexate and five hours after methotrexate infusion over a duration of one hour in a volume of 250 mL normal saline. . |
| Intervention |
TK-112690 |
The dose of TK-112690 is 45 mg/kg administered weekly for 4 consecutive weeks as an iv infusion one hour before methotrexate and five hours after methotrexate infusion over a duration of one hour in a volume of 250 mL normal saline. . |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
Male and female subjects over 18 years old with a histologically or cytological confirmed diagnosis of locally residual, recurrent or metastatic SCCHN.
Subject must have failed at least onecourses of non-MTX chemotherapy, orone course of non-MTX chemotherapyand chemo radiation for treating their SCCHN.
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 of 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.
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 in the patient’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
Est. creatinine clearance ≥45 mL/min
Total bilirubin ≤2.0 mg/dL (≤34.2 μmol/L)
AST & ALT ≤3 x ULN
Absolute granulocytes ≥1.5 x 109 cells/L
Platelets ≥100,000/µL
Be able to read orunderstand, and provide a signature or thumb impression on the Informed Consent Form (ICF) before entering the study.
|
|
| ExclusionCriteria |
| Details |
Subject has not failed at least onecourses of non-MTX chemotherapyor 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. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
|
|
Blinding/Masking
|
|
|
Primary Outcome
|
| Outcome |
TimePoints |
| Determine pilot efficacy of an iv infusion of TK-112690 to placebo as a mucositis preventive in subjects with locally advanced, residual, orrecurrent or metastatic SCCHN scheduled to receive MTX as chemotherapy. |
Patients will be evaluated for extent and severity of mucositis using established mucositis rating
scales, e.g., OMAS/Sonis, PROMS, WHO, and CTCAE/mucositis on the day prior to study start
(Day 0), and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on
Day 1 of Week 6. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Confirmation of the safety/tolerability of a continuous administered weekly for 4 weeks and lowering of plasma concentrations of surrogate markers of mucositis, e.g., CD40/CD40L, post TK-112690 in patients suffering from local, advanced, residual or recurrent, metastatic SCCHN receiving sequential continuous iv infusions of TK-112690 and MTX or TK-112690 placebo and MTX. |
Predose and postdose 24 hr and 28 hr safety samples for 4 week.6 week safety sample.also surrgoate Biomarkers at every week . |
|
|
Target Sample Size
|
Total Sample Size="22"
Sample Size from India="22"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="22" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
20/05/2019 |
| Date of Study Completion (India) |
02/10/2019 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="10"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
A review of a patient’s medical history including a detailed history of the patient’s cancer and concomitant medications will be performed at screening. Screening for drugs of abuse will be performed at the time of patient screening and Day 0 (the day before start of study). Vital sign measurements will be performed at patient screening, on Day 0, and at 24 and 48 hours post each initial infusion of TK-112690/placebo as well as on Day 1 of Week 6. Physical examinations will be performed at screening, on Day 0, and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6. ECOG performance status will be determined at patient screening, on Day 0, and at Day 1 of Weeks 6. For pre-menopausal females, a urine pregnancy test will be performed at screening, on Day 0, and at Day 1 of Week 6. 12-Lead ECG at screening and 24 hours post each initial infusion of TK-112690/ Placebo. CBC, Liver function test, Kidney function test determination at the clinical site prior to methotrexate treatment to ensure patient fitto dose. Serum chemistry, hematology, coagulation and urinalysis at screening, Day 0, and at 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6. Adverse events will be evaluated 5, 24 and 48 hours post each initial infusion of TK-112690/ Placebo as well as on Day 1 of Week 6. Blood samples will be obtained pre-initial infusion of TK-112690/ placebo and 5, 24 and 48 hours post each initial infusion as well as on Day 1 of Week 6. Plasma will be obtained from the blood samples in order to determine surrogate markers of mucositis, e.g., CD40/CD40L, TNF-α, etc. Patients will be evaluated for extent and severity of mucositis using established mucositis rating scales, e.g., OMAS/Sonis, PROMS, WHO, and CTCAE/mucositis on the day prior to study start (Day 0), and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6. Examination will assess the lining of the mouth, throat, and other linings of the digestive tract. Incidence of oral mucositis, duration of severe oral mucositis, throat soreness, severity of pain and use of parenteral or transdermal opioid analgesics will be assessed. |