CTRI/2023/05/052759 [Registered on: 17/05/2023] Trial Registered Prospectively
Last Modified On:
04/06/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Safety and Efficacy of Lenvatinib Capsules for the Treatment of Patients with Thyroid Cancer OR for the First Line Treatment of Patients with liver cancer
Scientific Title of Study
A Multi-Center, Single Arm, Phase IV Study to Assess the Safety and Efficacy of Lenvatinib Capsules for the Treatment of Patients with Locally Recurrent or Metastatic, Progressive, Radioactive Iodine-Refractory Differentiated Thyroid Cancer OR for the First Line Treatment of Patients with Unresectable Hepatocellular Carcinoma
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/21/001, Version No. 1.0, Dated 23/MAR/2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
AVP Head-India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
pravin.ghadge@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Shruti Saha
Designation
Manager India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
shruti.saha@sunpharma.com
Details of Contact Person Public Query
Name
Rajesh Gaikwad
Designation
Deputy General Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E) Mumbai 400063
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
rajesh.gaikwad@sunpharma.com
Source of Monetary or Material Support
Sun Pharmaceutical Industries Limited (SPIL)
Sun House, 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063
Primary Sponsor
Name
Sun Pharmaceutical Industries Limited (SPIL)
Address
Sun Pharmaceutical Industries Limited (SPIL)
Sun House, 201 B/1, Western Express Highway,
Goregaon ( E), Mumbai 400 063
Marathwada Regional Cancer Center and Research Institute
OPD No-37; Ground Floor, Department of Radiotherapy, Marathwada Regional Cancer Center and Research Institute (Govt. Cancer Hospital, Aurangabad [Unit of Govt. Medical College & Hospital, Aurangabad]), Kil-e-ark, Near Jama Masjid, Aurangabad. 431001 Aurangabad MAHARASHTRA
9850632639
bshewalkar.pi@gmail.com
Dr Srikrishna Mandal
NRS Medical College and Hospital
NRS Medical College and Hospital,
138, AJC Bose Road, Kolkata-700014
Kolkata WEST BENGAL
9830648931
mandal-srikrishna@rediffmail.com
Dr Vikas T Talreja
Regency Hospital LTD
Room No.02, 1st Floor, Regency Hospital LTD. Cancer and Gastro Care Centre, Tower 2, A 4, Sarvodaya Nagar, Kanpur-208005 U.P. India Kanpur Nagar UTTAR PRADESH
9769890961
vikasttalreja@gmail.com
Dr G Raja
Royapettah Medical College
Royapettah Medical College, Cancer Block, OPD, 1st Floor, West Cott Road, Royapettah, Chennai, Tamil Nadu 600014 Chennai TAMIL NADU
9841107677
rajaresearch17@gmail.com
Dr Tamohan Chaudhuri
Saroj Gupta Cancer Centre and Research Institute
1st Floor, Clinical Research Department, Mahatma Gandhi Road, Thakurpukur, Kolkata-700063 Kolkata WEST BENGAL
9830035796
clinicaltrialsgccri@gmail.com
Dr Mukesh Rulaniya
SMS Medical College and Attached Hospital
SMS Medical College and Attached Hospital,
JLN Marg, Jaipur, Rajasthan
India-302004
Jaipur RAJASTHAN
9413464059
mukeshrulaniya008@gmail.com
Dr Lokesh K N
SRV AGADI Hospital and Research Centre
Clinical Research Department, 1st Floor, 35, H Siddaiah Road, Wilson Garden, Bengaluru-560027, Karnataka, India Bangalore KARNATAKA
8971609070
drlokessrv@gmail.com
Dr Vishwateja Reddy
St. Ann’s General and Cancer Hospital
St. Ann’s General and Cancer Hospital 24-7-7/3, Fathima Nagar, Darga Road, Kazipet, Warangal Urban, Telangana 506004 Warangal TELANGANA
9963396668
drvishwateja.krcwgl@gmail.com
Dr P N Sathiyamoorthy
Stanley Medical College
Stanley Medical College
305, Old Jail Road, Chennai
Tamil Nadu, India. 600001
Chennai TAMIL NADU
8891576088
drsathiyamoorthy12@gmail.com
Dr Vikas Ostwal
Tata Memorial Centre/Hospital
Room No-319, 3rd Floor, Homi Bhaba building, tata Memorial hospital, Dr Ernest Borges Road, Parel, Mumbai-400012, Maharashtra, India Mumbai MAHARASHTRA
2224177000
dr.vikas.ostwal@gmail.com
Dr Jitendra Pehalajani
Vedanta Super Specialty Hospital
4th floor, Clinical Research Department
360, Near Kamla Devi Govt. School, Tagore Nagar,
Jaipur-302021, Rajasthan, India
Jaipur RAJASTHAN
Independent Ethics Committee Sumita Cancer Society, KINS Hospital
Approved
Institutional Ethics Committee, Saroj Gupta Cancer Centre and Research Institute
Submittted/Under Review
Institutional Ethics Committee_Vedanta Super Specialty Hospital
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Approved
Shah Lifeline Hospital and Heart Institute
Approved
SMS Medical College & Attached Hospital
Approved
St. Anns Institutionl Ethics Committee, (SATEGC)
Approved
Tata Memorial Centre/Hospital_TMH Institutional Ethics Committee-II
Submittted/Under Review
Tata Memorial Centre/Hospital_TMH Institutional Ethics Committee-I
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C220||Liver cell carcinoma,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Lenvatinib Capsules 4mg and 10mg
DTC: The recommended dosage of Lenvatinib is 24 mg orally once daily until disease progression or until unacceptable toxicity.
HCC: The recommended dosage of Lenvatinib is based on actual body weight: 12 mg for patients greater than or equal to 60 kg or 8 mg for patient less than 60 kg
Take Lenvatinib orally once daily until disease progression or until unacceptable toxicity
Comparator Agent
Not applicable
Not applicable
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
A. Criteria specific for DTC
1. Patients must have histologically or cytologically confirmed diagnosis of one of the following DTC subtypes:
a) Papillary thyroid cancer (PTC)
i. Follicular variant
ii. Variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin’s-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated)
b) Follicular thyroid cancer (FTC)
i. Hürthle cell
ii. Clear cell
iii. Insular
2. Measurable disease meeting the following criteria and confirmed by investigator assessment:
a) At least 1 measurable lesion according to The Revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
b) Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
3. Patients must show evidence of disease progression within 12 months (an additional month will be allowed to accommodate actual dates of performance of scans, i.e., within ≤ 13 months) according to RECIST 1.1 assessed and confirmed by review of CT and/or MRI scans
4. Patients must be 131I-refractory / resistant
5. Patients may have received either no or only one prior vascular endothelial growth factor (VEGF)/VEGFR-targeted therapy
6. HCC: The recommended dosage of Lenvatinib is based on actual body weight:
7. 12 mg for patients greater than or equal to 60 kg or
8. Take Lenvatinib orally once daily until disease progression or until unacceptable toxicity.
9. • Dosage Modifications for Adverse Reactions: Recommendations for Lenvatinib dose interruption,
10. reduction and discontinuation for adverse reactions are listed below:
11. Patients with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for one month
12. Patients must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be ≤ 5.0 mIU/L).
B. Criteria Specific for HCC:
1. Patients must have a confirmed diagnosis of HCC:
2. At least 1 measurable target lesion according to The Modified Revised Response Evaluation Criteria in Solid Tumors (mRECIST).
3. Patients is categorized to stage B [not applicable for Transarterial Chemoembolization (TACE)] or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
4. Patients with a Child-Pugh score A.
C. Common Criteria
1. Patients is willing to provide written informed consent
2. Male or female patients aged ≥ 18 and ≤ 75 years at the time of signing of the written informed consent.
3. All chemotherapy or radiation-related toxicities must have resolved to < Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE v 5.0), except alopecia and infertility
4. Patients has adequate hepatic, renal, bone marrow function and blood coagulation function.
5. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 140/90 mm Hg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
6. Adequate pancreatic function, defined as amylase and lipase ≤ 1.5 × ULN.
7. Patients with life expectancy of at least 12 weeks from the start of study treatment, as per Investigator’s judgment
8. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 – 2
9. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the patients must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
[Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal. Post-menopausal woman will be defined as: Woman not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age.]
10. Male patients must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation
ExclusionCriteria
Details
Patients will be deemed ineligible to participate in the study if he/she fulfils any of the following criteria:
A. Criteria specific for DTC
1. Anaplastic or medullary carcinoma of the thyroid
2. Any ongoing treatment for 131I-refractory DTC (exception TSH-suppressive thyroid hormone therapy) OR patients who have received any anticancer treatment within 21 days of Day 1.
3. History of Hep B or Hep C
B. Criteria specific for HCC
1. Patients with imaging findings for HCC corresponding to any of the following
• HCC with ≥ 50 percent liver occupation
• Clear invasion into the bile duct
• Portal vein invasion at the main portal branch (Vp4)
2. Patients who have received any systemic chemotherapy, including anti VEGF therapy, or any systemic investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note: Patients who have received local hepatic injection chemotherapy are eligible
3. Patients who have received any anticancer therapy or any blood enhancing treatment within 28 days prior to enrolment
4. Patients with arterial-portal venous shunt or arterial-venous shunt preventing a proper diagnosis of the tumour
5. Patients who have already undergone a liver transplant
C. Common Criteria:
1. Current or past history of bleeding OR thrombotic disorders
2. Current use of anticoagulants such as, warfarin or similar agents requiring therapeutic INR monitoring.
3. History of congestive heart failure (New York Heart association (NYHA) Class II to Class IV), unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment
4. Currently having Grade 3 or 4 cardiac dysfunction, gastrointestinal perforation, fistula formation or reversible posterior leukoencephalopathy syndrome
5. QTcF interval > 480 ms
6. History of major surgery within 3 weeks prior to the Day 1
7. Patients having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Patients with urine protein ≥ 1 g/24 h will be ineligible
8. Any medical or other condition (for example, gastrointestinal malabsorption, severe diarrhoea or any other condition that might affect the absorption of lenvatinib) which, in the opinion of the investigator, would preclude participation in a clinical trial
9. Currently having active infection (any infection requiring treatment)
10. Active malignancy (except for DTC/HCC respectively to indication or definitively treated melanoma in situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months
11. History of HIV
12. Participation in clinical trial of any investigational agent (drug or device) within 30 days prior to the first dose of study drug or planning during the study
13. Patients having intolerance, hypersensitivity or any contraindication to any of the study drug, other components or CT and MRI contrast agents.
14. Prior treatment with Lenvatinib
15. Current or recent substance abuse, including alcohol as per Diagnostic and Statistical Manual (DSM-5) criteria
16. Pregnant or lactating female
17. Patients has a clinically significant disorder that, in the opinion of the investigator, would result in the patient’s inability to understand and comply with the requirements of the study
18. Investigators, study personnel, sponsor representatives and their first degree relatives
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Proportion of patients with treatment emergent adverse events with Common Terminology Criteria for Adverse Events (CTCAE v 5.0) grade ≥ 3 [Timeframe: 24 weeks]
[Timeframe: 24 weeks]
Secondary Outcome
Outcome
TimePoints
A. Safety
• Proportion of patients with treatment emergent adverse events with CTCAE v 5.0 with any grade [Timeframe: 24 weeks]
• Proportion of patients requiring dose modifications (dose interruptions/ delays or dose reductions) [Timeframe: 24 weeks]
• Median time to first dose reduction [Timeframe: 24 weeks]
B. Efficacy
• Objective response rate (ORR) [Timeframe: 24 weeks]
 ORR was defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1 (DTC) or mRECIST (HCC)
• Proportion of patients with Progression-free survival (PFS) [Timeframe: 24 weeks]
 PFS: The time from the start of treatment until the first occurrence of disease progression or death, whichever is earlier
ORR and PFS will be measured by investigator assessment
24 weeks
Target Sample Size
Total Sample Size="104" Sample Size from India="104" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
This is a Phase IV, single arm, multicentre, open label study. The study will be conducted at 10-12 centres in India, having qualified Investigators. The study will be initiated only after the receipt of regulatory and ethics committee (EC) approval.
This period will be up to 21 days. Patients and/or her relatives will be explained about the entire scope of the research study and all the procedures of the study, along with the risks and the benefits to the patients, if they chose to participate in this study. After obtaining the written informed consent, patients will be screened by undergoing various assessments as mentioned in Schedule of Assessment (Appendix I). After confirming the eligibility, if the patients fulfils all the eligibility criteria, patients will be enrolled by allotting the enrolment number.
Treatment Period
This period will last for 169 days. The enrolled patients will consume the study medication, one tablet every day, continuously for 169 days. During the study, assessments will be performed as mentioned in Schedule of Assessment (Appendix I).
The study consists of following days of assessments:
Visit 1 - Day -21 to -1: Screening
Visit 2 – Day 1:
Visit 3 – Day 15 ± 4 Days:
Visit 4 – Day 29 ± 4 Days:
Visit 5 – Day 43 ± 4 Days:
Visit 6 – Day 57 ± 4 Days:
Visit 7– Day 85 ± 4 Days:
Visit 8 – Day 113 ± 4 Days:
Visit 9 – Day 141 ± 4 Days:
Visit 10 –Day 169 ± 4 Days:
Patients will be provided with diary to record details about study drug administration, adverse event details.
Patients discontinuing early from the study will be completing Visit 10 assessments. Visit 10 will be considered as end of treatment visit & end of study visit