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Phase II, Open-label, Study in Patients with anaplastic (ATC) or poorly differentiated thyroid carcinomas (PDTC) to investigate the Clinical Efficacy and Safety of the Combination Therapy of Lenvatinib and Pembrolizumab

Phase 2
Conditions
C73
Malignant neoplasm of thyroid gland
Registration Number
DRKS00013336
Lead Sponsor
niversitätsklinikum Freiburg
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Complete
Sex
All
Target Recruitment
36
Inclusion Criteria

1.Male or female patients aged >18 years without upper age limit
2.Patient with histologically confirmed anaplastic or poorly differentiated thyroid carcinoma
3.At least one measurable target lesion according to irRECIST meeting the following criteria:
•Lymph node (LN) lesion that measures at least 1 dimension as =1.5 cm in the short axis
•Non-nodal lesion that measures =1.0 cm in the longest diameter
•The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on irRECIST to be deemed a target lesion
4.ECOG performance status of 0-1
5.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =160/90 mmHg at screening and no change in antihypertensive medications within 1 week before registration.
6.Adequate renal function defined as creatinine =1.5xULN or calculated creatinine clearance =30 mL/min per the Cockcroft and Gault formula if creatinine level is >1.5xULN
7.Adequate bone marrow function defined by:
•Absolute neutrophil count (ANC) =1,000/µL
•Platelets =70,000/µL
•Hemoglobin =8 g/dL
8.Adequate blood coagulation function defined by International Normalized ratio (INR) =1.5
9.Adequate liver function defined by:
•Total bilirubin =1.5xULN except for unconjugated hyperbilirubinemia of Gilbert’s syndrome
•Alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3 xULN (in the case of liver metastases =5xULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. In case alkaline phosphatase is >3 xULN (in absence of liver metastases) or >5 xULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase
10.Written informed consent obtained according to international guidelines and local laws

Exclusion Criteria

1. Patients who have previously received lenvatinib for more than 4
weeks or pembrolizumab or any other immune checkpoint inhibitor
therapy (other kinase inhibitor therapies like sorafenib are permitted)
2. Patients with central nervous system (CNS) metastases, unless they
have completed local therapy and have discontinued the use of
corticosteroids for this indication for at least 1 week before starting
treatment in this study; any signs (e.g., radiologic) or symptoms of
brain metastases must be stable for at least 2 week before
registration.
3. Active other malignancy within the last two years life expectancy <1
year (except for ATC/PDTC) besides adequately treated local cancer
(skin cancer, prostate cancer, breast cancer without metastasis).
Antihormonal treatments besides aromatase inhibitors are allowed.
4. Known intolerance to study drug (or any of the excipients)
5. Radiation therapy within 14 days prior to start of study treatment with
the exception of palliative radiotherapy to bone lesions, which is
allowed if completed one day prior to the first intake of lenvatinib.

Study & Design

Study Type
interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
ORR obtained 12 weeks after start of treatment
Secondary Outcome Measures
NameTimeMethod
OS, PFS, CBR, duration of response (DOR), Quality of Life (QOL)
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