UMIN-CTR Clinical Trial

Public title

A study of prophylactic oral steroids for fatigue and malaise due to regorafenib treatment for unresectable metastatic colorectal cancer: a randomized, placebo-controlled, double-blind Phase 2 clinical study (KSCC1402/HGCSG1402)

Acronym

A study of prophylactic oral steroids for fatigue and malaise due to regorafenib treatment for unresectable metastatic colorectal cancer: a randomized, placebo-controlled, double-blind Phase 2 clinical study (KSCC1402/HGCSG1402)

Scientific Title

A study of prophylactic oral steroids for fatigue and malaise due to regorafenib treatment for unresectable metastatic colorectal cancer: a randomized, placebo-controlled, double-blind Phase 2 clinical study (KSCC1402/HGCSG1402)

Scientific Title:Acronym

A study of prophylactic oral steroids for fatigue and malaise due to regorafenib treatment for unresectable metastatic colorectal cancer: a randomized, placebo-controlled, double-blind Phase 2 clinical study (KSCC1402/HGCSG1402)

Region

Japan

Condition

Colorectal Cancer

Classification by specialty

Gastroenterology

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The objective of this randomized placebo-controlled Phase 2 study is to evaluate prophylactic effects of dexamethasone for fatigue and malaise (weakness, lethargy, malaise) resulting from regorafenib treatment, as well as to assess treatment continuation of regorafenib.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Incidence of fatigue or malaise (CTCAE ver. 4, all grades)

Key secondary outcomes

Brief Fatigue Inventory(Patient Reported Outcome),adverse events,relative dose intensity (regorafenib)

Exploratory endpoint : Compliance (regorafenib, study drug), response rate, disease control rate (DCR), treatment continuation period, progression-free survival (PFS), overall survival (OS)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Treatment group
Regorafenib 160mg
Once daily, 3weeks on, 1week off
plus
Study drug capsule
(Dexamethasone 2mg), once daily

Interventions/Control_2

Placebo group
Regorafenib 160mg
Once daily, 3weeks on, 1week off
plus
Placebo capsule
(Lactose), once daily

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) Patient is capable of granting informed consent in writing for receiving treatment outlined in this protocol.
2) The investigators determine that the patient can receive the treatment outlined in this protocol.
3) Patient has received histological diagnosis of adenocarcinoma of either the colon or the rectum (including anus), regardless of RAS mutation.
4) Patient has metastatic colorectal cancer that is scheduled for treatment with regorafenib.
5) Patient has lesions which are either measurable or non-measurable according to RECIST version 1.1.
6) Trunk part contrasting CT (the chest, epigastric region, pelvis) until 28 days before the registration. When contrasting CT is impossible for an allergy to contrast agents, the registration is possible only in trunk part simple CT.
7) Patient is at least 20 years of age.
8) PS(ECOG) 0-1
9) Patients for whom bone marrow, hepatic, and renal functions have all been confirmed as normal within 7 days prior to initiation of regorafenib treatment according to the following clinical test standards
Total bilirubin >= 2.0 mg/dL
AST <= 100 IU/L (;200 for patients with liver metastases)
ALT <= 100 IU/L (;200 for patients with liver metastases)
Creatinine <= 1.5mg/dL
Creatinine clearance >= 60mL/min
Persistent proteinuria of Grade 2 or lower according to NCI-CTCAE (ver. 4.0) (>3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
INR <= 1.5
Plt >= 100,000/ mm3
Hb >= 9.0g/dl
Neu >= 1,500/ mm3
10) Patients with life expectancy of at least 3 months

Key exclusion criteria

1) Patients who have used regorafenib previously.
2) Patients with Grade 2 or higher fatigue or malaise according to NCI-CTCAE (ver.4.0).
3) Patients with a history of a different type of cancer according to histological findings or cancer of a different primary focus within the past 5 years. However, the following are excluded: carcinoma in situ of the cervix, non-melanoma skin cancer, superficial bladder cancer (Ta, Tis, and T1), gastric cancer, non-invasive breast cancer, etc.
4) Patients who have undergone highly invasive surgery, an open biopsy, or who have received significant trauma within 28 days of initiating regorafenib treatment.
5) Patients with congestive cardiac failure of NYHA Class 2 or higher.
6) Patients with unstable angina (symptoms at rest),new-onset angina (onset within past 3 months), or a history of myocardial infarction within 6 months of initiating treatment.
7) Patients with arrhythmia requiring treatment with anti-arrhythmia drugs.
8) Patients with uncontrollable hypertension (systolic >150 mmHg or diastolic >90 mmHg even with hypotensives)
9) Patients with pleural effusion or ascites causing dyspnea (NCI-CTCAE (ver. 4.0) Grade 2 or higher).
10) Patients with a history of venous or arterial thrombosis or embolism within 6 months prior to initiation of treatment, including cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism.
11) Patients with active infections of NCI-CTCAE (ver. 4.0) Grade 3 or higher.
12) Patients positive for either HBs antigen or HCV antibody (testing required) HBc antibody test required prior to initiation of treatment.
33) Patients with other illnesses or conditions which, according to the judgment of the investigator, may result in physical harm caused by the study, or which may impair study compliance.

Target sample size

74

Name of lead principal investigator

1st name
Middle name
Last name	Hideo Baba

Organization

Graduate School of Life Sciences, Kumamoto University

Division name

Department of Gastroenterological Surgery

Zip code

Address

1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

TEL

096-373-5212

Email

kscc2@cres-kyushu.or.jp

Name of contact person

1st name
Middle name
Last name	Clinical Research Support Center Kyushu

Organization

KSCC Research Secretariat

Division name

KSCC Research Secretariat

Zip code

Address

3-1-1, Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan

TEL

092-631-2920

Homepage URL

https://www.ks-cc.jp

Email

kscc2@cres-kyushu.or.jp

Institute

Kyushu Study group of Clinical Cancer

Institute

Department

Personal name

Organization

Bayer Yakuhin, Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

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

熊本市民病院（熊本県）
慈泉会相澤病院（長野県）
光晴会病院（長崎県）
九州大学　消化器・総合外科，血液・腫瘍内科（福岡県）
九州大学病院別府病院（大分県）
済生会福岡総合病院（福岡県）
久留米大学（福岡県）
久留米大学医療センター（福岡県）
佐世保市立総合病院（長崎県）
長崎大学　移植・消化器外科（長崎県）
熊本大学（熊本県）
大分赤十字病院（大分県）
国立病院機構大分医療センター（大分県）
中津市立中津市民病院（大分県）
鹿児島厚生連病院（鹿児島県）
松山赤十字病院（愛媛県）
神戸市立医療センター中央市民病院（兵庫県）
岡山労災病院（岡山県）
JCHO九州病院（福岡県）
県立広島病院（広島県）
那覇市立病院（沖縄県）
獨協医科大学（栃木県）
薫風会佐野病院（兵庫県）
国立病院機構熊本医療センター（熊本県）
山口県立総合医療センター（山口県）
伊那中央病院（長野県）
立川綜合病院（新潟県）
苫小牧日翔病院（北海道）
札幌医科大学（北海道）
北海道がんセンター（北海道）
佐賀大学（佐賀県）
北海道大学（北海道）
国立病院機構九州医療センター（福岡県）
岐阜大学(岐阜県）
国立病院機構九州がんセンター（福岡県）
名古屋大学（愛知県）
釧路ろうさい病院（北海道）
埼玉県立がんセンター（埼玉県）
飯塚病院（福岡県）
中部徳洲会病院（沖縄県）
浜の町病院（福岡県）
香川大学（香川県）

Date of disclosure of the study information

2014

Year

09

Month

11

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

13th JSMO
Prophylactic Oral Steroids for Fatigue and Malaise due to Regorafenib : a Randomized Phase II trial (KSCC1402/HGCSG1402)
S.Yuki, Y.Miyamoto, Y.Emi, M.Shimokawa, S.Tokunaga, M.Nakamura, Y.Komatsu, T.Yamaguchi,H. Baba, Y. Maehara; Kyushu Study group of Clinical Cancer(KSCC), Hokkaido Gastrointestinal Cancer Study Group (HGCSG)

ASCO 2016
A randomized, double-blind, placebo-controlled phase II study of prophylactic dexamethasone therapy for fatigue and malaise due to regorafenib in patient with metastatic colorectal cancer: (KSCC1402/HGCSG1402)
Miyamoto Y, Yuki S, Shimokawa M, Tanioka H, Tsuji A, Asayama M, Shiraishi T, Kotaka M, Makiyama A, Komatsu Y, Masuda S, Yamaguchi T, Saeki H, Oki E, Emi Y, Baba H, Maehara Y, Kyushu Study Group of Clinical Cancer (KSCC)

ESMO-GI 2016
Updated report: A randomized, double-blind, placebo-controlled phase II study of prophylactic dexamethasone (dex) therapy for fatigue and malaise due to regorafenib in patient (pts) with metastatic colorectal cancer (mCRC):(KSCC1402/HGCSG1402)
Yuki S, Komatsu Y, Satake H, Miyamoto Y, Tanioka H, Tsuji A, Asayama M, Shiraishi T, Kotaka M, Makiyama A,Kashiwada T, Takeuchi N, Shimokawa M, Saeki H, Oki E, Emi Y, Baba H, Maehara Y;Kyushu Study group of Clinical Cancer (KSCC), Hokkaido Gastrointestinal Cancer Study Group (HGCSG)

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

2014

Year

08

Month

18

Day

Date of IRB

Anticipated trial start date

2014

Year

11

Month

04

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

09

Month

11

Day

Last modified on

2017

Year

04

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017600