Trial document




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  DRKS00013336

Trial Description

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Title

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

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Trial Acronym

ATLEP

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URL of the Trial

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Brief Summary in Lay Language

The aim of the study is to evaluate the efficacy and safety of a combination therapy of lenvatinib and pembrolizumab in ATC/PDTC patients and to establish the combination therapy as a new therapy standard after standard therapies/chemotherapy. In addition, the study will provide us with first indications of which biomarkers are predictive for response to therapy.

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Brief Summary in Scientific Language

The primary objective of the trial is to obtain first information on the efficacy of combination therapy of lenvatinib and pembrolizumab in patients with ATC or PDTC, measured as Objective Response Rate (ORR) obtained 12 weeks after start of the study treatment. Secondary objective is to assess Overall Survival (OS), Progression Free Survival (PFS), Clinical Benefit Rate (CBR), response duration and safety of combination therapy.

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Organizational Data

  •   DRKS00013336
  •   2019/05/16
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  •   yes
  •   Approved
  •   283/18 (Mono), Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   2017-004570-34 
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Health Condition or Problem studied

  •   C73 -  Malignant neoplasm of thyroid gland
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Interventions/Observational Groups

  •   In this study, patients receive continuous oral Lenvatinib therapy with a starting dose of 20 mg/day. This is combined with an i.v. immunocheckpoint inhibitor therapy with Pembrolizumab 200 mg absolute (every 3 weeks), starting 3 weeks after the start of Lenvatinib therapy. If side effects occur, the Lenvatinib dose can be gradually reduced to 10 mg/day.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   N/A
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Primary Outcome

ORR obtained 12 weeks after start of treatment

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Secondary Outcome

OS, PFS, CBR, duration of response (DOR), Quality of Life (QOL)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/05/28
  •   18
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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

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Exclusion Criteria

1.Patients who have previously received lenvatinib 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 with life expectancy <1 year (except for ATC/PDTC)
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.

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Addresses

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    • Universitätsklinikum Freiburg
    • Hugstetter Strasse 49
    • 79095  Freiburg
    • Germany
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    • UNIVERSITÄTSKLINIKUM FREIBURGKlinik für Innere Medizin I
    • Ms.  PD Dr.  Christine  Dierks 
    • Hugstetter Straße 55
    • 79106  Freiburg
    • Germany
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    • UNIVERSITÄTSKLINIKUM FREIBURGKlinik für Innere Medizin I
    • Ms.  PD Dr.  Christine  Dierks 
    • Hugstetter Straße 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Freiburg
    • Hugstetter Strasse 49
    • 79095  Freiburg
    • Germany
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    • Eisai GmbH
    • Lyoner Str. 36
    • 60528  Frankfurt/Main
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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