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
Phase 4
Recruiting
- Conditions
- Liver cell carcinoma,
- Registration Number
- CTRI/2023/05/052759
- Lead Sponsor
- Sun Pharmaceutical Industries Limited (SPIL)
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- All
- Target Recruitment
- 104
Inclusion Criteria
- 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).
- 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.
- 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.
Exclusion Criteria
- 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Measures
Name Time Method A. Safety •Proportion of patients with treatment emergent adverse events with CTCAE v 5.0 with any grade [Timeframe: 24 weeks]
Trial Locations
- Locations (19)
All India Institute of Medical Sciences (AIIMS)
🇮🇳Dehradun, UTTARANCHAL, India
Aman Hospital and Research Center
🇮🇳Vadodara, GUJARAT, India
Binayak Multi Speciality Hospital
🇮🇳Kolkata, WEST BENGAL, India
Erode Cancer Centre
🇮🇳Erode, TAMIL NADU, India
G.S.V.M. Medical College
🇮🇳Dehat, UTTAR PRADESH, India
HCG Manavata Cancer Centre
🇮🇳Nashik, MAHARASHTRA, India
KINS Hospital
🇮🇳Darjiling, WEST BENGAL, India
Kkasturi Medicare Pvt. Ltd
🇮🇳Thane, MAHARASHTRA, India
Marathwada Regional Cancer Center and Research Institute
🇮🇳Aurangabad, MAHARASHTRA, India
NRS Medical College and Hospital
🇮🇳Kolkata, WEST BENGAL, India
Scroll for more (9 remaining)All India Institute of Medical Sciences (AIIMS)🇮🇳Dehradun, UTTARANCHAL, IndiaDr Amit SehrawatPrincipal investigator9958474477dramitsehrawat@gmail.com