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

Conditions: Health Condition 1: C220- Liver cell carcinoma

Registration Number: CTRI/2023/05/052759

Lead Sponsor: Sun Pharmaceutical Industries Limited (SPIL)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

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

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,

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]Timepoint: [Timeframe: 24 weeks]

Secondary Outcome Measures

Name	Time	Method
A. Safety <br/ ><br>•Proportion of patients with treatment emergent adverse events with CTCAE v 5.0 with any grade [Timeframe: 24 weeks] <br/ ><br>•Proportion of patients requiring dose modifications (dose interruptions/ delays or dose reductions) [Timeframe: 24 weeks] <br/ ><br>•Median time to first dose reduction [Timeframe: 24 weeks] <br/ ><br>B. Efficacy <br/ ><br>•Objective response rate (ORR) [Timeframe: 24 weeks] <br/ ><br>?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) <br/ ><br>•Proportion of patients with Progression-free survival (PFS) [Timeframe: 24 weeks] <br/ ><br>?PFS: The time from the start of treatment until the first occurrence of disease progression or death, whichever is earlier <br/ ><br> <br/ ><br>ORR and PFS will be measured by investigator assessment <br/ ><br>Timepoint: 24 weeks