UMIN-CTR Clinical Trial

Public title

Multi-Center Phase II Clinical Trial on Efficacy and Safety of Everolimus in Patients with Unresectable or Metastatic Renal Cell Carcinoma after Failure of Treatment with 1st-Line TKI Therapy

Acronym

Efficacy and Safety of Everolimus in Patients with Unresectable or Metastatic Renal Cell Carcinoma after Failure of Treatment with 1st-Line TKI Therapy

Scientific Title

Multi-Center Phase II Clinical Trial on Efficacy and Safety of Everolimus in Patients with Unresectable or Metastatic Renal Cell Carcinoma after Failure of Treatment with 1st-Line TKI Therapy

Scientific Title:Acronym

Efficacy and Safety of Everolimus in Patients with Unresectable or Metastatic Renal Cell Carcinoma after Failure of Treatment with 1st-Line TKI Therapy

Region

Japan

Condition

Renal cell carcinoma

Classification by specialty

Urology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The objective of this study is to evaluate efficacy and safety of everolimus in patients with unresectable or metastatic renal cell carcinoma after failure of treatment with 1st-line TKI therapy.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

PFS

Key secondary outcomes

1) Overall survival from the initiation of TKI treatment as 1st-line therapy
2) Overall survival from the initiation of everolimus treatment
3) ORR
4) TTF
5) Safety profile
6) HRQOL

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

Everolimus 10 mg will be administered once daily under fasting condition. The dosage will be adjusted according to the discontinuation, reduction or withdrawal criteria due to adverse events.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients with unresectable or metastatic renal cell carcinoma who have confirmed histological or cytological diagnosis of clear cell renal cell carcinoma
2) Patients who received a singe agent of TKI treatment (sorafenib, sunitinib, pazopanib, axitinib) as 1st-line therapy and who meet all of the following criteria
- Patients with cancer progression during or after TKI treatment and who received the last dose of TKI within 8 weeks before enrollment
Disease progression is evaluated based on overall response using RECIST v.1.0; patients with PD are eligible for enrollment and investigator's assessment is also acceptable
- Patients who did not receive cytokine or chemotherapy 1 year prior to TKI treatment
- Patients who did not receive cytokine or chemotherapy as concomitant medication
3) Patients who have at least one measurable foci on CT or MRI
4) 18 years old or older
5) ECOG PS 0-1
6) No interstitial pneumonia in the lungs observed on chest CT
7) Patients with sufficient hematopoietic function who meet the following all criteria
- Neutrophil >= 1,500/mm3
- Platelet >= 10 times 104/mm3
- Hemoglobin > 9.0 g/dL
8) Patients with sufficient hepatic functions who meet the following all criteria
- Total-bilirubin <= 1.5 times ULN
- AST and ALT <= 2.5 times ULN (patients with hepatic metastasis <= 5.0 times ULN)
9) Patients with sufficient renal function who meet the following criterion
Serum creatinine <= 1.5 times ULN
10) Patients whose fasting blood glucose <= 1.5 times ULN and blood glucose level is under control
11) Patients who meet the following all criteria
- Total-cholesterol <= 400 mg/dL
- Triglycerides <= 5.0 times ULN
12) More than 3 months of life expectancy
13) Patients (or legal representative in case of minority) who gave informed consent for participation to the study after they received explanation of the briefing document

Key exclusion criteria

1) Patients with history of hypersensitivity against everolimus or sirolimus derivative
2) Pregnant, pregnancy suspect, nursing women, patients who plan to have a baby
3) Patients who are on long-term treatment with corticosteroid or immunosuppressant
4) Patients treated for another primary malignancy within 3 years of enrollment
5) Patients judged ineligible to participate in the study by the investigator

Target sample size

50

Name of lead principal investigator

1st name
Middle name
Last name	Seiichiro Ozono

Organization

Hamamatsu University School of Medicine

Division name

Department of Urology

Zip code

Address

1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, Japan

TEL

053-435-2306

Email

oznsei@hama-med.ac.jp

Name of contact person

1st name
Middle name
Last name	Takayuki Sugiyama

Organization

Hamamatsu University School of Medicine

Division name

Department of Urology

Zip code

Address

1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, Japan

TEL

053-435-2306

Homepage URL

Email

taka0311@hama-med.ac.jp

Institute

Japanese Afinitor Clinical Trial Group of RCC (J-ACTOR)

Institute

Department

Personal name

Organization

CSPOR

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

浜松医科大学(静岡県)
北海道大学(北海道)
札幌医科大学(北海道)
北海道がんセンター(北海道)
弘前大学(青森県)
秋田大学(秋田県)
岩手医科大学(岩手県)
筑波大学(茨城県)
自治医科大学(栃木県)
獨協医科大学(栃木県)
伊勢崎市民病院(群馬県)
埼玉医科大学国際医療センター(埼玉県)
防衛医科大学校(埼玉県)
千葉大学(千葉県)
千葉県がんセンター(千葉県)
帝京大学ちば医療センター(千葉県)
東京慈恵会医科大学附属柏病院(千葉県)
慶應義塾大学(東京都)
東京大学(東京都)
帝京大学(東京都)
日本医科大学(東京都)
東京女子医科大学(東京都)
東京女子医科大学東医療センター(東京都)
横浜市立大学(神奈川県)
横浜市立大学附属市民総合医療センター(神奈川県)
北里大学(神奈川県)
東海大学(神奈川県)
聖マリアンナ医科大学(神奈川県)
神奈川県立がんセンター(神奈川県)
信州大学(長野県)
藤田保健衛生大学(愛知県)
岐阜大学(岐阜県)
金沢大学(石川県)
京都大学(京都府)
大阪大学(大阪府)
近畿大学(大阪府)
大阪府立成人病センター(大阪府)
奈良県立医科大学(奈良県)
和歌山県立医科大学(和歌山県)
岡山大学(岡山県)
岡山医療センター(岡山県)
倉敷中央病院(岡山県)
広島大学(広島県)
広島市立広島市民病院(広島県)
山口大学(山口県)
徳島大学(徳島県)
香川大学(香川県)
高知大学(高知県)
九州大学(福岡県)
佐賀県医療センター好生館(佐賀県)
熊本大学(熊本県)
宮崎大学(宮崎県)
鹿児島大学(鹿児島県)

Date of disclosure of the study information

2010

Year

12

Month

22

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://www.ncbi.nlm.nih.gov/pubmed/28334974

Number of participants that the trial has enrolled

Results

A total of 57 patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus.
RESULTS:
The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70-6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1-20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13-11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77-5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%).
CONCLUSION:
The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2010

Year

12

Month

22

Day

Date of IRB

Anticipated trial start date

2011

Year

04

Month

01

Day

Last follow-up date

2015

Year

01

Month

11

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

12

Month

17

Day

Last modified on

2017

Year

06

Month

23

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005647