UMIN-CTR Clinical Trial

Public title

Phase I study of cetuximab plus U3-1565 in colorectal cancer with resistance to anti-EGFR antibody

Acronym

U3-1565-CRC P-I

Scientific Title

Phase I study of cetuximab plus U3-1565 in colorectal cancer with resistance to anti-EGFR antibody

Scientific Title:Acronym

U3-1565-CRC P-I

Region

Japan

Condition

Colorectal cancer

Classification by specialty

Medicine in general	Gastroenterology	Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate the recommended dose, safety and efficacy of cetuximab plus U3-1565 in KRAS wild-type colorectal cancer with resistance to anti-EGFR anitibody in a phase I study

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

Proportion of DLT(Dose limiting toxicity)

Key secondary outcomes

Pharmacokinetic parameters
Proportion and severity of adverse events
Response rate: RR
Duration of response: DOR
Disease control rate: DCR
Progression free survival: PFS
Overall survival: OS

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

Level1
First dose
Cetuximab: 400 mg/m2 div day1
U3-1565: 24 mg/kg div day1

From second dose on
Cetuximab: 250 mg/m2 div. day1,8
U3-1565: 16 mg/kg div day1
q2w

Level0
First dose
Cetuximab: 400 mg/m2 div day1
U3-1565: 16 mg/kg div day1

From second dose on
Cetuximab: 250 mg/m2 div day1,8
U3-1565: 12 mg/kg div day1,8
q2w

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) Histologically confirmed KRAS (EXON 2 codon12/13) wild-type colorectal adenocarcinoma
2) Unresectable colorectal cancer
3) Aged 20 years or over
4) ECOG Performance status (PS): 0, 1
5) 1 or more target lesions (RECIST ver 1.1)
6) Previous chemotherapy for unresectable colorectal cancer
1. received 5-FU
2. received oxaliplatin
3. received irinotecan
4. received cetuximab or panitumumab, and resistant to either
5. received 2 more regimens
7) Adequate organ function as evidenced by the following laboratory studies within 14 days prior to enrollment
1. Neutrophil count: 1,200/mm3 or above
2. Hemoglobin: 8.0 g/dL or above
3. Platelet count: 75000/mm3 or above
4. Total bilirubin: 2.0 mg/dL or less
5. AST (GOT): 100 IU/L or less
6. ALT (GPT): 100 IU/L or less
7. Serum creatinin: 2.0 mg/dL or less
8) No blood transfusion within 14 days prior to enrollment
9) Grade 1 or less of acute adverse events or recovered to the baseline before the previous treatment
10) Not pregnant in lactating female
11) Written infromed consent

Key exclusion criteria

1) Any chemotherapy within 2 weeks prior to enrollment
2) Any surgery or radiation within 4 weeks prior to enrollment
3) Any investigatilnal drug within 4 weeks prior to enrollment
4) Previous administration of U3-1565
5) Hypersensitivity to U3-1565 or its additives
6) Metastasis to central nervous system
7) Pleural effusion, ascites or pericardial effusion under drainage
8) Other currently active malignancies excluding malignancies that are disease free for more than 3 years or carcinoma-in -situ deemed cured by adequate treatment
9) History of any severe medical condition
10) HBs Ag: positive, HCV Ab: positive
11) Continuous systemic steroids or immunosuppressant drug
12) Active bleeding
13) No contraception
14) No will or impossible to follow the protocol
15) Investigator considered the patients inappropriate to the trial.

Target sample size

23

Name of lead principal investigator

1st name	Takako
Middle name
Last name	Nakajima

Organization

St. Marianna University School of Medicine Hospital

Division name

Department of Medical Oncology

Zip code

216-8511

Address

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

TEL

0449778111

Email

tnakajima@marianna-u.ac.jp

Name of contact person

1st name	Takako
Middle name
Last name	Nakajima

Organization

St. Marianna University School of Medicine Hospital

Division name

Department of Medical Oncology

Zip code

216-8511

Address

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

TEL

0449778111

Homepage URL

Email

tnakajima@marianna-u.ac.jp

Institute

St. Marianna University School of Medicine Hospital

Institute

Department

Personal name

Organization

DAIICHI SANKYO COMPANY, LIMITED

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

St. Marianna University School of Medicine Hospital

Address

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

Tel

044-977-8111

Email

tnakajima@marianna-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

聖マリアンナ医科大学病院　

Date of disclosure of the study information

2014

Year

03

Month

01

Day

URL releasing protocol

https://www.ncbi.nlm.nih.gov/pubmed/31020609

Publication of results

Published

URL related to results and publications

https://www.ncbi.nlm.nih.gov/pubmed/31020609

Number of participants that the trial has enrolled

22

Results

No dose-limiting toxicities were observed among three patients in level 1 in the first stage, which was determined as RD.

Results date posted

2020

Year

02

Month

03

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

This phase I study of U3-1565, anti-HB-EGF antibody, and Cetu combination therapy enrolled patients with KRAS wild-type metastatic colorectal cancer who had received two or more regimens with fluoropyrimidine, oxaliplatin, irinotecan, and Cetu/Pani and had disease progression on Cetu/Pani.

Participant flow

Recommended dosewas determined in the 1st stage, followed by evaluation of efficacy at the RD level in the 2nd-stage. Cetu was given at a loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2 in levels 1 and 0. U3-1565 was administered at a loading dose of 24 mg/m2 followed by biweekly infusions of 16 mg/m2 in level 1 and 16-12 mg/m2 in level 0. Twenty-two patients were enrolled.

Adverse events

Grade 3 or higher adverse events occurred in 59.1 percent; those in 5% or more of patients were anemia, GTP elevation, and acneiform rash.

Outcome measures

Overall response rate was 0.0% [95% confidence interval (CI): 0.0%-15.4%] and disease control was achieved in 17 patients (77.3%, 95% CI: 54.6%-92.2%). Median progression-free survival time was 85.0 days (95% CI: 54.0-91.0) and median survival time was 196 days (95% CI: 113.0-306.0). RD was determined as level 1. The efficacy of this combination therapy after progression on Cetu/Pani was negligible.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

12

Month

04

Day

Date of IRB

2014

Year

02

Month

01

Day

Anticipated trial start date

2014

Year

03

Month

19

Day

Last follow-up date

2014

Year

12

Month

05

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

01

Month

29

Day

Last modified on

2020

Year

02

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015097