UMIN-CTR Clinical Trial

Public title

A multi-center proof-of-concept phase2 study of encorafenib + binimetinib + cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer

Acronym

BIG BANG Study

Scientific Title

A multi-center proof-of-concept phase2 study of encorafenib + binimetinib + cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer

Scientific Title:Acronym

BIG BANG Study

Region

Japan

Condition

Colorectal cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To evaluate the clinical efficacy, safety, and proof-of-concept (POC) of combination therapy consisting of BRAF inhibitor (encorafenib), MEK inhibitor (binimetinib), and an anti-epidermal growth factor receptor (EGFR) antibody (cetuximab) in patients with BRAF non-V600E mutated metastatic CRC.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Confirmed objective response rate by investigators' assessment

Key secondary outcomes

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

Combination therapy of encorafenib + binimetinib+ cetuximab
One cycle is 28 days.
Binimetinib: 45 mg, twice daily, oral
Encorafenib: 300 mg, once daily, oral
Cetuximab: 400 mg/m2 for initial dose, 250 mg/m2 for subsequent doses, weekly, intravenous infusion

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

Patients who meet all of the inclusion criteria A and B, and do not fall under the any of exclusion criteria will be enrolled as patients for study treatment.
At least 8 patients with lesions eligible for biopsy should be enrolled in the primary analysis parts; biopsy of lesions of which measurement in accordance with the RECIST version 1.1 is performed is accepted.


Inclusion criteria A
1.Age of 20 years or older on the day of signing informed consent
2.Confirmed diagnosis of advanced (unresectable) or metastatic colorectal cancer (mCRC) by tissue diagnosis
3.Patients who did not respond to or tolerate at least one chemotherapy regimen (including irinotecan or oxaliplatin) containing fluoropyrimidine drugs in the treatment of metastatic CRC, and are thus eligible for second or later line treatment
4.RAS wild-type and BRAF non-V600E mutated CRC. The diagnosis should be based on the results of associated genetic tests, and the record should be available
5.Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

Inclusion criteria B:
1.Measurable lesions in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
2.Patients with the adequate organ functions
3.Adequate cardiac function characterized by the following at screening
1)Left ventricular ejection fraction (LVEF) over 50% as determined by a MUGA scan or ECHO;
2)Mean triplicate QT interval corrected for heart rate using Fridericia's formula (QTcF) value less than 480 msec
4.Women of childbearing potential who are negative in a urine pregnancy test
5.Female patients and male patients must agree to take appropriate precautions to avoid pregnancy from the day of signing informed consent through 90 days after the final administration of investigational drugs.

Key exclusion criteria

1.History of treatment with epidermal growth factor receptor (EGFR) inhibitors including anti-EGFR antibody drugs
2.History of treatment with BRAF inhibitors or MEK inhibitors
3.History of treatment with regorafenib
4.Symptomatic brain metastases or meningeal dissemination
5.Leptomeningeal disease
6.Medical history, current condition, or risk of retinal vein occlusion
7.Inadequately controlled diabetes requiring insulin therapy
8.Acute or chronic pancreatitis
9.Medical history of clinically significant cardiac diseases
10.Gastrointestinal function or gastrointestinal diseases that significantly interfere with absorption, distribution, metabolism, and excretion of the study drugs
11.No history of other malignant tumors within 3 years before the start of study treatment. In cases of lesions corresponding to carcinoma in situ and intramucosal carcinoma judged to be cured by local therapy, non-metastatic prostate cancer not requiring systemic therapy, and other solid cancers that do not require therapy or are not estimated to be adversely affected by the study treatment, patients will not be excluded from the study when the coordinating committee concludes after consultation that there is no effect on the patient's prognosis.
12.Medical history of thromboembolism within 6 months
13.Concurrent neuromuscular disorder that is associated with the potential of elevated CK
14.Previous treatment with any of the following,
a.cyclical chemotherapy within a period of 14 days
b.bevacizumab, aflibercept, or ramucirumab within 3 weeks
c.biologic therapy (except bevacizumab, aflibercept, or ramucirumab), immunotherapy, marketed small molecular compounds, or non marketed investigational anticancer treatments within 4 weeks, or within a period 5fold the halflife (whichever is shorter)
d.prior radiotherapy to 30% of bone marrow

Target sample size

36

Name of lead principal investigator

1st name
Middle name
Last name	Hideaki Bando

Organization

National Cancer Center Hospital East

Division name

Department of Gastrointestinal Oncology

Zip code

Address

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

TEL

04-7133-1111

Email

BIGBANG_core@east.ncc.go.jp

Name of contact person

1st name
Middle name
Last name	Daisuke Kotani

Organization

National Cancer Center Hospital East

Division name

Department of Gastrointestinal Oncology

Zip code

Address

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

TEL

04-7133-1111

Homepage URL

Email

BIGBANG_core@east.ncc.go.jp

Institute

National Cancer Center Hospital Eas

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Government offices of other countries

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

愛知県がんセンター中央病院　(愛知県)、国立がん研究センター東病院（千葉県）、九州がんセンター(福岡県)、四国がんセンター(愛媛県)、北海道大学病院(北海道)、聖マリアンナ医科大学病院(神奈川県)

Date of disclosure of the study information

2018

Year

04

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

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

No longer recruiting

Date of protocol fixation

2018

Year

02

Month

22

Day

Date of IRB

2018

Year

04

Month

18

Day

Anticipated trial start date

2018

Year

05

Month

15

Day

Last follow-up date

2023

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

03

Month

23

Day

Last modified on

2023

Year

07

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036377