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Phase II Study Assessing the Efficacy and Safety of Lenvatinib for Anaplastic Thyroid Cancer

Phase 2
Completed
Conditions
Anaplastic Thyroid Cancer
Interventions
Registration Number
NCT02726503
Lead Sponsor
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Brief Summary

The purpose of this phase Ⅱ study is to assess the efficacy and safety of lenvatinib for anaplastic thyroid cancer patients who are diagnosed as unresectable. The total duration of the study will be 30 months. All patients will start administration of lenvatinib within 1 week of enrollment and receive the study drug 24mg orally once daily at almost the same time. 1 cycle consists of 4 weeks. Treatment term starts on the day 1st of drug administration of cycle 1 and administration will be continued until patients meet withdrawal criteria. Safety and efficacy assesment will be conducted on a regular basis during the trial. Tumor evaluation will be conducted at 4weeks, 8 weeks, 12 weeks, 16 weeks and at every 8 weeks after the 16th week since initial administration. When study drug administration terminated,tests of the drug termination will be conducted within 7 days of withdrawal and final observation will be conducted at 30 days after the last dose. Survival survey will be conducted at follow-up term. After the termination of the study drug, survival follow up survey will be conducted every 12 weeks unless patients withdraw enrollment of this study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
39
Inclusion Criteria
  1. Histologically confirmed as anaplastic thyroid cancer

  2. Unresectable disease

  3. Have measurable lesion defined by the RECIST version 1.1

  4. Have adequate organ function and meet following laboratory value:

    1. Bone marrow function test within 14 days prior to enrollment:

      neutrophil count>=1.5 x 103/microL blood platelet count>=10.0 x 104/microL hemoglobin amount>=9.0 g/dL

    2. Liver function test within 14 days prior to enrollment:

      AST,ALT<=3.0 x ULN(without liver metastatic) AST,ALT<=5.0 x ULN(with liver metastatic) bilirubin<=2.0 mg/dL

    3. Kidney function test within 14 days prior to enrollment:

      GFR estimation>=50 ml/min/1.73 m2 GFR estimation calculated by following formula. Male:194 x(serum creatinine concentration)-1.094 x(Age)-0.287 Female:Male GFR estimation x 0.739

    4. Cardiac function test within 28 days prior to enrollment: 12-lead electrocardiogram: no clinically important abnormality as shown below: heart disease, severe arrhythmia etc.

  5. Regardless of usage of antihypertensive drug, systolic blood pressure <=140 mm Hg and diastolic blood pressure <=90 mm Hg (If already taking antihypertensive drug, must have capacity of further antihypertensive therapy.)

  6. ECOG performance status 0-2

  7. Ability to swallow oral medications

  8. Life expectancy greater than 8 weeks

  9. Have signed written informed consent to participate in this study

Exclusion Criteria
  1. Have complications or medical history of

    1. Complication of brain metastasis (Exclude if cured and in clinically stable condition for more than 1 month prior to screening.)
    2. Treatment required complication of systemic infectious disease
    3. Complication of pulmonary fibrosis or interstitial pneumonitis
    4. Medical history of clinically significant cardiovascular disease within 6 months of initial dose as: NYHA class above 2 leveled congestive heart failure, unstable angina, cardiac infarction or cardiac arrhythmia with paroxysmal or required treatment e) Uncontrollable complication of diabetes mellitus f) hemoptysis within 3 weeks of enrollment (blood volume of more than half of teaspoon) g) Medical history of hemorrhagic or thrombotic disease within 6 months of enrollment h) If proteinuria values above 2+ by urinary protein qualitative test, conduct 24-hour urine collection and the urine protein determined as 1g/24 hours or more. (can substitute to the ratio of proteinuria in morning urine/creatinine) i) Malabsorption at gastrointestinal tract and any of the complication diseases that investigator considers that will be affected to lenvatinib absorption j) Recent major surgery within 2 weeks (if needle biopsy within 1 week) of enrollment k) Drainage required celomic fluid stagnation
  2. Have history of lenvatinib administration

  3. Confirmed tumor invasion to the carotid arteries

  4. Have history of high dose external radiation therapy to cervical region, and irradiated tumor location close to the carotid arteries.

  5. Have any unresolved toxicity greater than 1 by CTCAE v4.0.

  6. Have active double cancer

  7. Female patients who are pregnant, lactating, breast feeding or have childbearing potential

  8. Psychiatric disorder and regarded by the investigator as inadequate for this study enrollment

  9. Confirmed as no resistance to any component of this drug

  10. Currently receiving other interventional clinical study treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment ArmLenvatinib-
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)up to 30 months

OS is defined as time frame from date of initial dose until date of death from any cause. Or until the last confirmed survival date, study cut-off date which ever comes first.

Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)up to 30 months

PFS is defined as time frame from date of initial dose until the date of first confirmed disease progression, until date of death from any cause or the last tumor evaluating date whichever comes first.

Best Overall Response (BOR)up to 30 months

BOR is defined as the best total efficacy record during the date of initial dose to the date of study completion, by which evaluated with following index. Complete Response (CR), Partial Response (PR), Stable Disease (SD is defined as ≧3 weeks),Pharmacodynamics/Progressive Disease (PD) or Not Evaluable (NE).

Objective Response Rate (ORR)up to 30 months

ORR is defined as the ratio of patients who are evaluated as CR or PR in Best Overall Response (BOR).

Clinical Benefit Rate (CBR)up to 30 months

CBR is defined as the ratio of patients who are evaluated as CR, PR or durable SD (dSD is defined as ≧11 weeks SD) in Best Overall Response (BOR).

Disease Control Rate (DCR)up to 30 months

DCR is defined as the ratio of patients who are evaluated as CR, PR or SD in Best Overall Response (BOR).

Safety assessment on the incidence ratio of adverse eventsup to 30 months

Safety assessment will be assessed by the ratio of adverse event

Trial Locations

Locations (23)

Nagoya University Hospital

🇯🇵

Nagoya-city, Aichi-prefecture, Japan

Kuma Hospital

🇯🇵

Kobe-city, Hyogo-prefecture, Japan

IUHW Ichikawa Hospital

🇯🇵

Ichikawa-city, Chiba-prefecture, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Koto-ku, Tokyo-metropolis, Japan

Japanese Red Cross Narita Hospital

🇯🇵

Narita-city, Chiba-prefecture, Japan

Fujita Health University Hospital

🇯🇵

Toyoake-city, Aichi-prefecture, Japan

National Cancer Center Hospital East

🇯🇵

Kashiwa-city, Chiba-prefecture, Japan

University of Tsukuba Hospital

🇯🇵

Tsukuba-city, Ibaraki-prefecture, Japan

Kobe Univbersity Hospital

🇯🇵

Kobe-city, Hyogo-prefecture, Japan

Iwate Medical University Hospital

🇯🇵

Morioka-city, Iwate-prefecture, Japan

Kitasato University Hospital

🇯🇵

Sagamihara-city, Kanagawa-prefecture, Japan

Miyaghi Cancer Center

🇯🇵

Natori-city, Miyagi-prefecture, Japan

Showa University Northern Yokohama Hospital

🇯🇵

Yokohama-city, Kanagawa-prefecture, Japan

Kanagawa Cancer Center

🇯🇵

Yokohama-city, Kanagawa-prefecture, Japan

Shinsyu University School of Medicine Department of Surgery

🇯🇵

Matsumoto-city, Nagano-prefecture, Japan

Tohoku University Hospital

🇯🇵

Sendai-city, Miyagi-prefecture, Japan

Nara Hospital Kinki University Faculty of Medicine

🇯🇵

Ikoma-city, Nara-prefecture, Japan

Nara Medical University

🇯🇵

Kashihara-city, Nara-prefecture, Japan

Osaka Police Hospital

🇯🇵

Osaka-city, Osaka-prefecture, Japan

Osaka City University Graduate School of Medicine and Faculty of Medicine

🇯🇵

Osaka-city, Osaka-prefecture, Japan

Nippon Medical School Hospital

🇯🇵

Bunkyo-ku, Tokyo-metropolis, Japan

Ito Hospital

🇯🇵

Shibuya-ku, Tokyo-metropolis, Japan

Tokyo Medical University Hospital

🇯🇵

Shinjuku-ku, Tokyo-metropolis, Japan

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