UMIN-CTR Clinical Trial

Recruitment status Completed
Unique ID issued by UMIN UMIN000013006
Receipt No. R000015097
Scientific Title Phase I study of cetuximab plus U3-1565 in colorectal cancer with resistance to anti-EGFR antibody
Date of disclosure of the study information 2014/03/01
Last modified on 2020/02/03 (Ver. 8)

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Basic information
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
Condition Colorectal cancer
Classification by specialty
Medicine in general Gastroenterology Hematology and clinical oncology
Classification by malignancy Malignancy
Genomic information NO

Objectives
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

Assessment
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

Base
Study type Interventional

Study design
Basic design Single arm
Randomization Non-randomized
Randomization unit
Blinding Open -no one is blinded
Control Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute St. Marianna University School of Medicine Hospital
Institute
Department

Funding Source
Organization DAIICHI SANKYO COMPANY, LIMITED
Organization
Division
Category of Funding Organization Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
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
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions 聖マリアンナ医科大学病院　

Other administrative information
Date of disclosure of the study information
2014 Year 03 Month 01 Day

Related information
URL releasing protocol https://www.ncbi.nlm.nih.gov/pubmed/31020609
Publication of results Published

Result
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

Progress
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
Other related information

Management information
Registered date
2014 Year 01 Month 29 Day
Last modified on
2020 Year 02 Month 03 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000015097