UMIN-CTR Clinical Trial

Public title

Cetuximab plus S-1 and irinotecan (IRIS) as first-line treatment in RAS wild type metastatic colorectal cancer, a phase I/II trial (KSCC1401)

Acronym

Cetuximab plus S-1 and irinotecan (IRIS) as first-line treatment in RAS wild type metastatic colorectal cancer, a phase I/II trial (KSCC1401)

Scientific Title

Cetuximab plus S-1 and irinotecan (IRIS) as first-line treatment in RAS wild type metastatic colorectal cancer, a phase I/II trial (KSCC1401)

Scientific Title:Acronym

Cetuximab plus S-1 and irinotecan (IRIS) as first-line treatment in RAS wild type metastatic colorectal cancer, a phase I/II trial (KSCC1401)

Region

Japan

Condition

Colorectal cancer

Classification by specialty

Gastroenterology

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Determine maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan when combined with S-1 and cetuximab (Phase I), then investigate the safety profile and efficacy of the RD (Phase II) in patients with RAS wild type metastatic colorectal cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I,II

Primary outcomes

Phase I: maximum tolerated dose (MTD) and recommended dose (RD)
Phase II: objective response rate

Key secondary outcomes

Phase I: safety profile (incidence of adverse events and the severity)
Phase II: overall survival, progression-free survivial, and the safety profile (incidence of adverse events and the severity)

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

Phase I: IRIS + cetuximab
S-1 80-120mg day1-14
Irinotecan 120-150mg/m2 day1
Cetuximab 250mg/m2 day1,8,15
(initial dose:400mg/m2)
administered every 3 weeks until PD
Phase II: IRIS + cetuximab
Administered the RD fixed in Phase I

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) Signed written informed consent
2) Diagnosis of histologically confirmed metastatic adenocarcinoma of the colon or rectum (not anal canal cancer)
3) Inoperable, and no previous systemic chemotherapy
4) RAS mutation analysis
5) Unidimensionally measurable disease (RECIST ver.1.1 criteria) in truncal site (between chest and pelvis) by contrast enhanced CT. Baseline CT scan must be performed within 28 days prior to registration.
6) ECOG performance status of 0 or 1
7) Between 20-75 of age at informed consent (Phase I)
>=20 years of age at study informed consent (Phase II)
8) Life expectancy of at least 3 months
9) Oral intake possible
10) Baseline laboratory tests within 14 days prior to registration.:
i) Neutrophils >= 1,500/mm3
ii) Platelet count >= 100,000/mm3
iii) Hemoglobin >= 9 g/dL
iv) Total bilirubin <= 1.5 mg/dL
v) AST <= 100 IU/L (<= 200 IU/L in case of liver metastasis)
vi) ALT <= 100 IU/L (<= 200 IU/L in case of liver metastasis)
vii) Creatinine clearance >= 60 mL/min
11) UGT1A1 genotype tested:
*6*28 wild (G/G), or *6*28 hetero (G/A)

Key exclusion criteria

1) History of severe hypersensitivity reaction to any drugs
2) Synchronous or metachronous double cancer other in the last 5 years except early stage cancers which can be treated with a local treatment.
3) Symptomatic peripheral neuropathy >= grade 1
4) Severe dysesthesia or paresthesia with functional disorder
5) Diarrhea >= grade 2
6) Clinically relevant infectious diseases (active infection with body temperature; higher or equal to 38 degree)
7) Clinically relevant psychiatric or neurological condition including dementia which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication
8) Symptomatic brain metastasis
9) Severe complicating disorders (e.g. diabetes that is poorly controlled, uncontrolled high blood pressure, hepatic cirrhosis, hepatic failure, renal failure, interstitial pneumonia, pulmonary fibrosis, intestinal paralysis, ileus, cardiac disease)
10) Treatment with a blood product or hematopoietic growth factors (e.g. G-CSF) within 14 days prior to registration
11) Requiring treatment for ascites or pleural effusion
12) Congenital bleeding disorders or blood coagulopathy
13) Requiring ongoing treatment with a contraindicated concomitant medication (e.g. flucytosine, or phenytoin, warfarin potassium)
14) Previous radiotherapy for the primary lesion or any metastasis
15) Concurrent chronic systemic steroid treatment
16) Known history of hypersensitivity reaction to irinotecan
17) Previous exposure to cetuximab, irinotecan or S-1 therapy
18) Ongoing treatment with atazanavir sulphate
19) Hepatitis B surface antigen (HBsAg) or hepatitis-C virus (HCV) antibody positive
20) Any geographic or social circumstances or psychological or medical disorder, which, in the investigator's opinion, does not allow the patient to complete the study

Target sample size

57

Name of lead principal investigator

1st name
Middle name
Last name	Tadashi Nishimaki

Organization

University of the Ryukyus Faculty of Medicine

Division name

Division of Digestive and General Surgery

Zip code

Address

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

TEL

092-631-2920

Email

sakamoto.kscc@gmail.com

Name of contact person

1st name
Middle name
Last name	KSCC

Organization

Clinical Research Support Center Kyushu

Division name

KSCC

Zip code

Address

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

TEL

092-631-2920

Homepage URL

Email

sakamoto.kscc@gmail.com

Institute

Kyushu Study group of Clinical Cancer(KSCC)

Institute

Department

Personal name

Organization

Merck Serono

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

国立病院機構九州医療センター（福岡県）
済生会福岡総合病院（福岡県）
製鉄記念八幡病院（福岡県）
社会保険田川病院（福岡県）
社会保険仲原病院（福岡県）
久留米大学 外科/がん集学治療センター，腫瘍センター（福岡県）
長崎大学　移植・消化器外科（長崎県）
光晴会病院（長崎県）
熊本大学（熊本県）
JCHO人吉医療センター（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）
中頭病院（沖縄県）
琉球大学（沖縄県）
松山赤十字病院（愛媛県）
長崎みなとメディカルセンター 市民病院（長崎県）
田主丸中央病院（福岡県）
薫風会佐野病院（兵庫県）
国立病院機構福岡東医療センター（福岡県）
九州大学　消化器・総合外科（福岡県）
公立学校共済組合九州中央病院（福岡県）
国立病院機構別府医療センター（大分県）
田川市立病院（福岡県）
九州大学病院別府病院（大分県）
鹿児島大学（鹿児島県）
神戸市立医療センター中央市民病院（兵庫県）
那覇市立病院（沖縄県）
久留米大学（福岡県）
済生会八幡総合病院（福岡県）
長崎大学　腫瘍外科（長崎県）
佐賀県医療センター好生館（佐賀県）
浦添総合病院（沖縄県）
大分県立病院（大分県）
JCHO九州病院（福岡県）
公立八女総合病院（福岡県）
国立病院機構長崎医療センター（長崎県）
南風病院（鹿児島県）
済生会川内病院（鹿児島県）
広島赤十字・原爆病院（広島県）
獨協医科大学（栃木県）
高野会大腸肛門病センター高野病院（熊本県）
医理会柿添病院（長崎県）
山口県立総合医療センター（山口県）
今給黎総合病院（鹿児島県）

Date of disclosure of the study information

2014

Year

12

Month

03

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

11

Month

27

Day

Date of IRB

Anticipated trial start date

2014

Year

12

Month

03

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

12

Month

03

Day

Last modified on

2019

Year

03

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018427