UMIN-CTR Clinical Trial

Public title

Phase II study assessing the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE)

Acronym

HOPE

Scientific Title

Phase II study assessing the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE)

Scientific Title:Acronym

HOPE

Region

Japan

Condition

Anaplastic thyroid cancer

Classification by specialty

Endocrinology and Metabolism

Endocrine surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The purpose of this study is to investigate the efficacy and safety of lenvatinib in patients with unresectable anaplastic thyroid cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase II

Primary outcomes

Overall Survival (OS)

Key secondary outcomes

1) Progression-Free Survival (PFS)
2) Best Overall Response (BOR)
3) Objective Response Rate (ORR)
4) Disease Control Rate (DCR)
5) Clinical Benefit Rate (CBR)
6) Safety assessment on the incidence ratio of adverse events

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

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.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1)Histologically confirmed as anaplastic thyroid cancer
2) Unresectable anaplastic thyroid cancer
3) Have measurable lesion defined by the RECIST version 1.1
4) Have adequate organ function and meet following laboratory value:
(a) 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
(b) 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
(c) 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
(d) 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

Key exclusion criteria

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

Target sample size

39

Name of lead principal investigator

1st name	Iwao, Makoto
Middle name
Last name	Sugitani, Tahara

Organization

Graduate School of Medicine Nippon Medical School, National Cancer Center Hospital East

Division name

Department of Endocrine Surgery, Division of Head and Neck Medical Oncology

Zip code

113-8603,277-8577

Address

1-1-5 Sendagi Bunkyo-ku Tokyo 113-8603, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577 Japan

TEL

03-5814-6219(04-7133-1111)

Email

isugitani@nms.ac.jp

Name of contact person

1st name	Iwao, Makoto
Middle name
Last name	Sugitani, Tahara

Organization

Graduate School of Medicine Nippon Medical School, National Cancer Center Hospital East

Division name

Department of Endocrine Surgery, Division of Head and Neck Medical Oncology

Zip code

113-8603, 277-8577

Address

1-1-5 Sendagi Bunkyo-ku Tokyo 113-8603, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577 Japan

TEL

03-5814-6219(04-7133-1111)

Homepage URL

Email

isugitani@nms.ac.jp

Institute

Translational Research Informatics Center, Foundation for Biomedical Research and Innovation

Institute

Department

Personal name

Organization

Eisai Co.,Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

National Cancer Center Hospital East

Address

6-5-1 Kaashiwanoha, Kashiwa

Tel

04-7133-1111

Email

matahara@east.ncc.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2016

Year

01

Month

28

Day

URL releasing protocol

none

Publication of results

Published

URL related to results and publications

https://doi.org/10.1016/j.ejca.2022.06.044

Number of participants that the trial has enrolled

52

Results

Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis and 50 patients were included for safety analysis. The estimated 1-year OS rate was 11.9% (95% CI, 4.4% to 23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an ORR of 11.9%, DCR of 73.8%, and CBR of 33.3%.

Results date posted

2024

Year

11

Month

01

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Median age was 73.0 years (39 to 89). Females were predominant (71.4%). Most patients had a good performance status (ECOG-PS 0-1: 92.9%) and half had stage IVC disease (47.6%). The study population included initially unresectable locally advanced disease and unresectable locally advanced or metastatic disease after surgical resection.Fifteen patients (35.7%) received curative surgical resection for ATC, while 8 (19.0%) received noncurative surgical resection. Seventeen patients (40.5%) had received previous chemotherapy with weekly paclitaxel and 9 (21.4%) had received radiotherapy. One patient had previously received radioactive iodine.

Participant flow

A total of 52 patients from 17 institutions participating in the ATCCJ were enrolled from April 2016 to December 2018. Follow-up ended on February 25, 2020. Two patients were excluded from safety analysis because they withdraw consent for the study before the first administration, leaving 50 patients included in the safety analysis. One tumor specimen was not sent to pathological review. Of the 49 patients evaluated by the central pathology review board, 5 patients were diagnosed as having thyroid cancer which was pathologically different from ATC and two patients were not definitively diagnosed as having ATC. Finally, 42 patients were confirmed to have ATC and included in the efficacy analysis.

Adverse events

AEs of any grade were observed in 45 patients (90.0%). The most frequent AEs included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and the palmar-plantar erythrodysesthesia syndrome (26.0%). Treatment-related AEs (TRAEs) were observed in 43 patients (86.0%). Twenty-seven patients (54.0%) developed serious AEs. During protocol treatment, 7 patients (14.0%) died due to severe AEs, including respiratory failure, peritoneal carcinomatosis, skin ulcer, and acute heart failure. Among these events, acute heart failure was considered a treatment-related AE, while the others were considered the results of rapid exacerbation of the protocol disease.

Outcome measures

The primary endpoint for efficacy was OS, defined as time from the date of first administration to the date of death from any cause. The secondary endpoints were PFS, defined as time from the date of first dose to the first documentation of disease progression as determined by investigator assessment, or death, whichever occurred first; best overall response, defined as best response recorded from the date of the first dose until disease progression/recurrence as determined by investigator assessment, or death, whichever occurred first; objective response rate (ORR), defined as the proportion of patients with a complete or partial response; disease control rate (DCR), defined as the proportion of patients with complete or partial response, or stable disease, where stable disease must last 3 weeks for ATC; and clinical benefit rate (CBR), defined as the proportion of patients with complete or partial response, or durable stable disease, defined as stable disease lasting 11 weeks for ATC.
The safety of lenvatinib in patients with ATC was measured by the occurrence of adverse events (AEs), changes in laboratory results (including urinalysis, hematology, and blood chemistry), vital signs, weight, electrocardiography, and PS. Assessment of AEs was completed using the Medical Dictionary for Regulatory Activities, and AEs were graded using Common Terminology Criteria for AEs (CTCAE) version 4.0.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

10

Month

22

Day

Date of IRB

2015

Year

11

Month

27

Day

Anticipated trial start date

2016

Year

01

Month

04

Day

Last follow-up date

2019

Year

12

Month

07

Day

Date of closure to data entry

2020

Year

03

Month

01

Day

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

01

Month

28

Day

Last modified on

2024

Year

11

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023862