UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000011294
Receipt number	R000013232
Scientific Title	Randomized Phase II Study of Regorafenib followed by Cetuximab versus Reverse SequenCe for Wild-Type KRAS Metastatic Colorectal Cancer Previously Treated with Fluoropyrimidine, Oxaliplatin, and Irinotecan (REVERECE)
Date of disclosure of the study information	2013/09/30
Last modified on	2017/09/19 14:14:56

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Basic information

Public title

Randomized Phase II Study of Regorafenib followed by Cetuximab versus Reverse SequenCe for Wild-Type KRAS Metastatic Colorectal Cancer Previously Treated with Fluoropyrimidine, Oxaliplatin, and Irinotecan (REVERECE)

Acronym

Randomized Phase II Study of Sequential Treatment of Regorafenib and Cetuximab for colorectal cancer (REVERCE)

Scientific Title

Scientific Title:Acronym

Randomized Phase II Study of Sequential Treatment of Regorafenib and Cetuximab for colorectal cancer (REVERCE)

Region

Japan

Condition

Colorectal cancer

Classification by specialty

Gastroenterology

Classification by malignancy

Malignancy

Genomic information

Objectives

Narrative objectives1

This is a randomized phase II study designed to evaluate the efficacy and safety of sequential treatment with regorafenib (Treatment 1) followed by cetuximab +/- irinotecan (Treatment 2) (Arm A) for wild-type KRAS metastatic colorectal cancer after treatment failure with or intolerable to chemotherapy including fluoropyrimidine, oxaliplatin, and irinotecan as compared with sequential treatment with cetuximab +/- irinotecan) (Treatment 1) followed by regorafenib (Treatment 2) (Arm B) with exploratory analysis for biomarkers.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Assessment

Primary outcomes

Overall survival

Key secondary outcomes

time to sequential treatment failure (TTF), progression-free survival (PFS) of sequential therapy, PFS of Treatment 1 and Treatment 2, response rate of Treatments 1 and Treatment 2, disease control rate of Treatments 1 and Treatment 2, incidence of adverse events , pateints reported outcome of QOL

Base

Study type

Interventional

Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

Concealment

Central registration

Intervention

No. of arms

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

sequential treatment with regorafenib followed by cetuximab +/- irinotecan

Interventions/Control_2

sequential treatment with cetuximab +/- irinotecan followed by regorafenib

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

90 years-old >=

Gender

Male and Female

Key inclusion criteria

1)Histologically proven, unresectable distant metastatic or locally advanced colorectal adenocarcinoma
2)No KRAS mutation (codon 12 & 13) (i,e, wild-type KRAS): KRAS test will be performed at the study site or an external institution using an appropriate technique such as direct-sequence, Scorpions and ARMS, TaqMan Mutation Detection Assays or Luminex.
3)-5)PD or intolerable to chemotherapy including fluoropyrimidine*, L-OHP* and CPT-11 *
* Disease progression or intolerable to chemotherapy are defined as those who meet any of the following:
i)Radiographically confirmed recurrence during or within 6 months after adjuvant therapy
ii)Radiographically or clinically confirmed disease progression during or within 3 months after chemotherapy for advanced cancer
iii)Unacceptable toxicity precluding resumption of treatment
6) Evaluable lesion(s)
a) Measurable lesion(s) is not mandatory
b) Excluding patients with only body cavity fluid, bone metastasis, skin metastasis, pulmonary lymphangiosis, radiographically undetectable abdominal mass, or cystic lesion
7)>= 20 years at the time of informed consent
8)ECOG PS: 0-1
9)Adequate organ functions within 7 days before enrollment (excluding blood transfusion or hematopoietic factor preparations such as G-CSF within 14 days before enrollment)
-Neutrophil count: >= 1500/mm3
-Hb: >=8.0 g/dL (blood transfusion more than 2 weeks before is allowed)
-Plt count:>7.5 x 104/mm3
-AST, ALT: <= ULN x 2.5 <= ULN x 5 in patients with liver metastasis)
-Total bilirubin: <= ULN x 1.5
-Creatinine: <= 1.5 mg/dL
-Protein urine
i) Protein urine (urine dipstick) <= 2+ or
ii) UPC ratio <3.5 or
iii)24-hour protein urine <= 3500 mg
-PT-INR: <= ULN x 1.5 (<= x3in the subjects with anticoagulants)
10)Expected to survive for at least 60 days after entry
11)At least 2 weeks of washout from previous radiotherapy and/or chemotherapy for the underlying disease
12)Written consent after detailed explanation of the study before entry including consent for QOL and BMs

Key exclusion criteria

1)Previous treatment with regorafenib, anti-EGFR antibody (cetuximab/panitumumab) or participation in clinical trial for regorafenib
2)Poorly controlled hypertension (SBP>150 mmHg or DBP >90 mmHg despite appropriate treatment)
3)Unstable angina, myocardial infarction, brain infarction, or pulmonary embolism within 6 months before entry
4)Body cavity fluid (e.g., pleural effusion, ascites, pericardial fluid) requiring intervention
5)Local or systemic active infection (grade 3 or higher according to the CTCAE ver. 4) requiring intervention
6)Symptomatic brain metastasis or brain metastasis requiring regular medication (e.g., mannitol, steroids, antiepileptic drugs)
7)Intestinal paralysis or severe gastrointestinal obstruction
8)Patients unable to swallow oral medications
9)Grade 3 or higher hemorrhage within 4 weeks before entry
10)History or clear evidence in CT scanof extensive interstitial pulmonary disease (e.g., interstitial pneumonia, pulmonary fibrosis)
11)Heart failure ≥ NYHA II
12)History of meningitis carcinomatosis, uncontrollable seizures (status epilepticus, intractable epilepsy), clinically significant mental disorder, or central nerve disorder
13)Active hepatitis B or C
14)Other active malignancies that may affect the prognosis
15)Pregnant or possibly pregnant women, lactating women, or patients unwilling to use adequate contraception
16)Uncontrolled diarrhea (diarrhea interfering with daily life despite appropriate treatment)
17)Unhealed wound (excluding central venous port), ulcer, or bone fracture
18)Any major surgery. open biopsy or traumatic injury within 28 days before enrollment (excluding the same day of the week 4 weeks ago) or colostomy without intestinal resection within 14 days before enrollment
19)Daily systemic steroid treatment (for such as collagen disease)
20)Known hypersensitivity to study drugs, study drug classes, or excipients in the formulation
21)Patients who, in the opinion of the investigator, are inappropriate for the study

Target sample size

180

Research contact person

Name of lead principal investigator

1st name

Middle name

Last name Takayuki Yoshino

Organization

National Cancer Center Hospital East

Division name

Department of Gastroenterology and Gastrointestinal Oncology

Zip code

Address

6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan

TEL

04-7133-1111

Email

kshitara@east.ncc.go.jp

Public contact

Name of contact person

1st name

Middle name

Last name Kohei Shitara

Organization

National Cancer Center Hospital East

Division name

Department of Gastroenterology and Gastrointestinal Oncology

Zip code

Address

6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan

TEL

04-7133-1111

Homepage URL

Email

kshitara@east.ncc.go.jp

Sponsor or person

Institute

REVERCE study group

Institute

Department

Personal name

Funding Source

Organization

Bayer Yahin Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Other related organizations

Co-sponsor

Name of secondary funder(s)

IRB Contact (For public release)

Organization

Address

Tel

Email

Secondary IDs

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

REVERCE参加施設

Other administrative information

Date of disclosure of the study information

2013 Year 09 Month 30 Day

Related information

URL releasing protocol

Publication of results

Unpublished

Result

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

Progress

Recruitment status

No longer recruiting

Date of protocol fixation

2013 Year 07 Month 25 Day

Date of IRB

Anticipated trial start date

2013 Year 11 Month 15 Day

Last follow-up date

2017 Year 08 Month 07 Day

Date of closure to data entry

2017 Year 09 Month 10 Day

Date trial data considered complete

2017 Year 09 Month 10 Day

Date analysis concluded

Other

Other related information

Management information

Registered date

2013 Year 07 Month 26 Day

Last modified on

2017 Year 09 Month 19 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013232

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name