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

Sponsor

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan (Other)

Overall Status

Completed

CT.gov ID

NCT02726503

Collaborator

(none)

Enrollment

Locations

Arm

47.5

Actual Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Thyroid Cancer	Drug: Lenvatinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 4, 2016

Actual Primary Completion Date :

Feb 25, 2020

Actual Study Completion Date :

Mar 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm	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.

Arm

Intervention/Treatment

Experimental: Treatment Arm

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.

Outcome Measures

Primary Outcome Measures

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

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).
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).
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).
Safety assessment on the incidence ratio of adverse events [up to 30 months]
Safety assessment will be assessed by the ratio of adverse event

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed as anaplastic thyroid cancer
Unresectable disease
Have measurable lesion defined by the RECIST version 1.1
Have adequate organ function and meet following laboratory value:
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

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

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

Cardiac function test within 28 days prior to enrollment: 12-lead electrocardiogram: no clinically important abnormality as shown below: heart disease, severe arrhythmia etc.
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.)
ECOG performance status 0-2
Ability to swallow oral medications
Life expectancy greater than 8 weeks
Have signed written informed consent to participate in this study

Exclusion Criteria:

Have complications or medical history of
Complication of brain metastasis (Exclude if cured and in clinically stable condition for more than 1 month prior to screening.)
Treatment required complication of systemic infectious disease
Complication of pulmonary fibrosis or interstitial pneumonitis
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)

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

Have history of lenvatinib administration
Confirmed tumor invasion to the carotid arteries
Have history of high dose external radiation therapy to cervical region, and irradiated tumor location close to the carotid arteries.
Have any unresolved toxicity greater than 1 by CTCAE v4.0.
Have active double cancer
Female patients who are pregnant, lactating, breast feeding or have childbearing potential
Psychiatric disorder and regarded by the investigator as inadequate for this study enrollment
Confirmed as no resistance to any component of this drug
Currently receiving other interventional clinical study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya University Hospital	Nagoya-city	Aichi-prefecture	Japan	466-8560
2	Fujita Health University Hospital	Toyoake-city	Aichi-prefecture	Japan	470-1192
3	IUHW Ichikawa Hospital	Ichikawa-city	Chiba-prefecture	Japan	272-0827
4	National Cancer Center Hospital East	Kashiwa-city	Chiba-prefecture	Japan	277-8577
5	Japanese Red Cross Narita Hospital	Narita-city	Chiba-prefecture	Japan	286-8523
6	Kuma Hospital	Kobe-city	Hyogo-prefecture	Japan	650-0011
7	Kobe Univbersity Hospital	Kobe-city	Hyogo-prefecture	Japan	650-0017
8	University of Tsukuba Hospital	Tsukuba-city	Ibaraki-prefecture	Japan	305-8576
9	Iwate Medical University Hospital	Morioka-city	Iwate-prefecture	Japan	020-8505
10	Kitasato University Hospital	Sagamihara-city	Kanagawa-prefecture	Japan	252-0375
11	Showa University Northern Yokohama Hospital	Yokohama-city	Kanagawa-prefecture	Japan	224-8503
12	Kanagawa Cancer Center	Yokohama-city	Kanagawa-prefecture	Japan	241-8515
13	Miyaghi Cancer Center	Natori-city	Miyagi-prefecture	Japan	981-1293
14	Tohoku University Hospital	Sendai-city	Miyagi-prefecture	Japan	980-8574
15	Shinsyu University School of Medicine Department of Surgery	Matsumoto-city	Nagano-prefecture	Japan	390-8621
16	Nara Hospital Kinki University Faculty of Medicine	Ikoma-city	Nara-prefecture	Japan	630-0293
17	Nara Medical University	Kashihara-city	Nara-prefecture	Japan	634-8522
18	Osaka Police Hospital	Osaka-city	Osaka-prefecture	Japan	543-0035
19	Osaka City University Graduate School of Medicine and Faculty of Medicine	Osaka-city	Osaka-prefecture	Japan	545-8585
20	Nippon Medical School Hospital	Bunkyo-ku	Tokyo-metropolis	Japan	113-8603
21	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo-metropolis	Japan	135-8550
22	Ito Hospital	Shibuya-ku	Tokyo-metropolis	Japan	150-8308
23	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo-metropolis	Japan	160-0023

Sponsors and Collaborators

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan

Investigators

Study Director: Iwao Sugitani, M.D., Ph.D, Graduate School of Medicine Nippon Medical School
Study Director: Makoto Tahara, M.D., Ph.D, National Cancer Center Hospital East