| CTRI Number |
CTRI/2017/05/008587 [Registered on: 17/05/2017] Trial Registered Prospectively |
| Last Modified On: |
25/07/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Radiation Therapy
Preventive
Process of Care Changes
Other (Specify) [Mucositis] |
| Study Design |
Non-randomized, Active Controlled Trial |
|
Public Title of Study
|
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 of Study
|
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 |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CLP-2690-0002 Version 02 05/09/2016 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Mr A Kiran Kumar |
| Designation |
Head - Operations |
| Affiliation |
CRBio ( A Division of RA CHEM PHARMA) |
| Address |
RA CHEM PHARMA LTD CLINICAL RESEARCH AND BIOSCIENCES DIVISION Plot no 26 and 27, Technocrat Industrial Estate Balanagar
Hyderabad
ANDHRA PRADESH
500037
India
Hyderabad
ANDHRA PRADESH
500037
India |
| Phone |
04044758595 |
| Fax |
04044758596 |
| Email |
kirankumar@crbio.co.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr L Krishna Murthy |
| Designation |
Head Clinical Operations |
| Affiliation |
CRBio ( A Division of RA CHEM PHARMA) |
| Address |
RA CHEM PHARMA LTD CLINICAL RESEARCH AND BIOSCIENCES DIVISION Plot no 26 and 27, Technocrat Industrial Estate Balanagar
Hyderabad
ANDHRA PRADESH
500037
India
Hyderabad
ANDHRA PRADESH
500037
India |
| Phone |
04044758595 |
| Fax |
04044758596 |
| Email |
drmurthy@crbio.co.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sagar Bhosale |
| Designation |
Manager - Clinical |
| Affiliation |
CRBio ( A Division of RA CHEM PHARMA) |
| Address |
RA CHEM PHARMA LTD CLINICAL RESEARCH AND BIOSCIENCES DIVISION Plot no 26 and 27, Technocrat Industrial Estate Balanagar
Hyderabad
ANDHRA PRADESH
500037
India
Hyderabad
ANDHRA PRADESH
500037
India |
| Phone |
04044758595 |
| Fax |
04044758596 |
| Email |
drsagar@crbio.co.in |
|
|
Source of Monetary or Material Support
|
| Tosk,Inc.
2672 Bayshore Parkway, Suite 507
Mountain View, CA 94043 |
|
|
Primary Sponsor
|
| Name |
Tosk Inc |
| Address |
2672 Bayshore Parkway, Suite 507
Mountain View, CA 94043 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Kirankumar Jadhav |
B.J. Medical College & Sassoon General Hospital |
Oncology Department
Sassoon General Hospital Sassoon Road, Pune, Maharashtra
Pune
MAHARASHTRA |
02026128000
drkirankumarj@gmail.com |
| Dr Mohammad Athar |
G.S.V.M College |
Oncology Department-Hospital Swaroop Nagar, Kanpur,Uttar Pradesh
Kanpur Nagar
UTTAR PRADESH |
9839313534
atharonco92@yahoo.com |
| Dr Vibhore Mahendru |
M.V. Hospital and Research Center |
Oncology Department 314/30 Mirza Mandi, Chowk, Lucknow, Uttar Pradesh
Lucknow
UTTAR PRADESH |
05222258215
mvhrclko@gmail.com |
| Dr BhushanTapiramNemade |
Manas Hospital |
Oncology Deptparment, Opp Tupsakhare Lawns, Mumbai Naka, Nashik, Maharashtra
Nashik
MAHARASHTRA |
9766126132
02532573721
drbtnemade@yahoo.co.in |
| Dr Rakesh Neve |
Sanjeevan Hospital |
302,Oncology Department , Plot No. 23, Off Karve road, Erandawane, Pune, Maharashtra
Pune
MAHARASHTRA |
9881143140
rakesh.neve@gmail.com |
| Dr Neha Gupta |
Sudbhawana Hospital |
Oncology Department B-31/80, 23 B, Bhogabir, Lanka, Varanasi
Varanasi
UTTAR PRADESH |
9450282031
singhjai82@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee G.S.V. M. Medical College |
Not Applicable |
| Ethics Committee Sanjeevan Hospital |
Approved |
| IEC of B. J. GOVT. MEDICAL COLLEGE & SASSOON GENERAL HOSPITALS |
Approved |
| Institutional Ethics Committee for M.V. Hospital and Research Center |
Approved |
| MANAS HOSPITAL ETHICS COMMITTEE |
Approved |
| Sudbhawana Hospital Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Squamous Cell Carcinoma of Head and Neck, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Not Applicable |
Not Applicable |
| Intervention |
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 |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
• 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 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
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
|
|
| ExclusionCriteria |
| Details |
• 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
|
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Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 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-112690 |
24 hrs,48 hrs of 1 to 4 week and week 5 and week 8 for Mucositiis Assessment |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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 the |
after PK,Biomarkers and surrogate Markers assessment |
|
|
Target Sample Size
|
Total Sample Size="25"
Sample Size from India="25"
Final Enrollment numbers achieved (Total)= "25"
Final Enrollment numbers achieved (India)="25" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
05/06/2017 |
| Date of Study Completion (India) |
29/06/2018 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
none yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
Review
of a patient’s medical history including a detailed history of the
patient’s cancer and concomitant medications will be performed at
screening. · A screen for drugs of abuse and alcohol will be performed at screening and Day 0 (day before start of study). · Vital
sign measurements at screening, on Day 0, and at 24 and 48 hours post
each initial infusion of TK-112690 as well as on Day 1 of Week 5 and 8. · Physical
examinations will be performed at screening, on Day 0, and 24 and 48
hours post each initial infusion of TK-112690 as well as on Day 1 of
Week 5 and 8. · ECOG performance status will be determined at Screening, on Day 0 and at Day 1 of Week 5 and 8. · For pre-menopausal females, urine pregnancy test at screening, on Day 0 and at Day 1 of Week 5 and 8. - 12-Lead ECG at screening and 24 hours post each initial infusion of TK-112690
- Serum
chemistry, hematology, coagulation and urinalysis at Day 0 and at
24 and 48 hours post each initial infusion of TK-112690 as well as
on Day 1 of Week 5 and 8.
- Adverse
events will be evaluated 5, 24 and 48 hours post each initial
infusion of TK-112690 formulation as well as on Day 1 of Week 5
and 8.
- Blood
samples will be obtained pre initial infusion of TK-112690 and 5
and 24 hours post each initial infusion of TK-112690. Plasma will
be obtained from the blood samples and analyzed for TK-112690.
- Blood
samples will be obtained pre initial infusion of TK-112690 and 5
and 24 hours post each initial infusion of TK-112690. Plasma will
be obtained from the blood samples and analyzed for uridine, a
biomarker of TK-112690 activity.
- Blood
samples will be obtained pre initial infusion of TK-112690 and 5,
24 and 48 hours post each initial infusion as well as on Day 1 of
Week 5 and 8. Plasma will be obtained from the blood samples and
analyzed for markers indicative of mucositis, eg, CD40/CD40L.
- Mucositis
will be evaluated for extent and severity of mucositis using
established mucositis rating scales, eg, OMAS/Sonis, PROMS, WHO
and CTCAE/mucositis on the day
prior to study start (Day 0), and 5, 24 and 48 hours post each
initial infusion of TK-112690 or TK-112690 formulation as well as
on Day 1 of Week 5 and 8. Examination will assess the
lining of the mouth, throat or 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.
|