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

Anaplastic Thyroid Cancer Clinical Trial

— HOPE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02726503
• Other study ID #: TRIHN1504
• Secondary ID: UMIN000020773
• Status: Completed
• Phase: Phase 2
• Start date: April 4, 2016
• Est. completion date: March 20, 2020

Study information

• Verified date: June 2020
• Source: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: March 20, 2020
• Est. primary completion date: February 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anaplastic Thyroid Cancer
• Thyroid Carcinoma, Anaplastic
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Lenvatinib
All patients will receive lenvatinib 24 mg orally once daily at almost the same time. The treatment will be started within 1 week after enrollment. 1 cycle consists of 4 weeks. The administration will be continued until patients meet withdrawal criteria. If any toxicity manifested that cannot be ruled out causal association with the study drug, drug withdrawal or dosage reduction will be conducted in accordance with drug withdrawal/dosage reduction criteria.

Locations

Country	Name	City	State
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo-metropolis
Japan	IUHW Ichikawa Hospital	Ichikawa-city	Chiba-prefecture
Japan	Nara Hospital Kinki University Faculty of Medicine	Ikoma-city	Nara-prefecture
Japan	Nara Medical University	Kashihara-city	Nara-prefecture
Japan	National Cancer Center Hospital East	Kashiwa-city	Chiba-prefecture
Japan	Kobe Univbersity Hospital	Kobe-city	Hyogo-prefecture
Japan	Kuma Hospital	Kobe-city	Hyogo-prefecture
Japan	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo-metropolis
Japan	Shinsyu University School of Medicine Department of Surgery	Matsumoto-city	Nagano-prefecture
Japan	Iwate Medical University Hospital	Morioka-city	Iwate-prefecture
Japan	Nagoya University Hospital	Nagoya-city	Aichi-prefecture
Japan	Japanese Red Cross Narita Hospital	Narita-city	Chiba-prefecture
Japan	Miyaghi Cancer Center	Natori-city	Miyagi-prefecture
Japan	Osaka City University Graduate School of Medicine and Faculty of Medicine	Osaka-city	Osaka-prefecture
Japan	Osaka Police Hospital	Osaka-city	Osaka-prefecture
Japan	Kitasato University Hospital	Sagamihara-city	Kanagawa-prefecture
Japan	Tohoku University Hospital	Sendai-city	Miyagi-prefecture
Japan	Ito Hospital	Shibuya-ku	Tokyo-metropolis
Japan	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo-metropolis
Japan	Fujita Health University Hospital	Toyoake-city	Aichi-prefecture
Japan	University of Tsukuba Hospital	Tsukuba-city	Ibaraki-prefecture
Japan	Kanagawa Cancer Center	Yokohama-city	Kanagawa-prefecture
Japan	Showa University Northern Yokohama Hospital	Yokohama-city	Kanagawa-prefecture

Sponsors (1)

Lead Sponsor	Collaborator
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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.	up to 30 months
Secondary	Progression-Free Survival (PFS)	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.	up to 30 months
Secondary	Best Overall Response (BOR)	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).	up to 30 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the ratio of patients who are evaluated as CR or PR in Best Overall Response (BOR).	up to 30 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the ratio of patients who are evaluated as CR, PR or SD in Best Overall Response (BOR).	up to 30 months
Secondary	Clinical Benefit Rate (CBR)	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).	up to 30 months
Secondary	Safety assessment on the incidence ratio of adverse events	Safety assessment will be assessed by the ratio of adverse event	up to 30 months