UMIN-CTR Clinical Trial

Basic information
Public title	A phase III, randomized, controlled study of mFOLFOX6 + bevacizumab combination therapy versus mFOLFOX6 + panitumumab combination therapy in chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable, advanced/recurrent colorectal cancer
Acronym	PARADIGM study
Scientific Title	A phase III, randomized, controlled study of mFOLFOX6 + bevacizumab combination therapy versus mFOLFOX6 + panitumumab combination therapy in chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable, advanced/recurrent colorectal cancer
Scientific Title:Acronym	PARADIGM study
Region	Japan

Condition
Condition	colorectal cancer
Classification by specialty	Hematology and clinical oncology Hepato-biliary-pancreatic surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	o verify the efficacy of mFOLFOX6 + panitumumab combination therapy and mFOLFOX6 + bevacizumab combination therapy in first-line treatment of chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable, advanced/recurrent colorectal cancer.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase III

Assessment
Primary outcomes	1. Overall survival (OS) 2. OS for Participants with Left-sided Tumors
Key secondary outcomes	Efficacy Progression-free survival (PFS) Response rate (RR) Duration of response (DOR) Percentage of subjects treated with surgical resection after chemotherapy(complete resection) Safety Percentage of subjects with adverse events

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	mFOLFOX6 + panitumumab
Interventions/Control_2	mFOLFOX6 + bevacizumab
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	80 years-old >
Gender	Male and Female
Key inclusion criteria	(1)Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol. (2)Patients who have given written consent to take part in the study after detailed explanation of the study prior to enrollment (3)Aged 20 to <80 years at the time of informed consent (4)Patients with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer) (5)Patients with lesion(s) that can be evaluated. (6)Patients who have not received chemotherapy for colorectal cancer. Patients who experience relapse more than 24 weeks (168 days) after the final dose of perioperative adjuvant chemotherapy* with fluoropyrimidine agents may be enrolled. *: Patients who have received perioperative adjuvant chemotherapy including oxaliplatin are excluded. (7)Patients classified as KRAS/NRAS wild-type by KRAS/NRAS testing. KRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146) NRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61),EXON4 (codon 117, 146) (8)Patients who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment 1)Neutrophil count >= 1.5x103/micro;L 2)Platelet count >= 1.0x104/micro;L 3)Hemoglobin >= 9.0 g/dL 4)Total bilirubin <= 2.0 mg/dL 5)AST <= 100 IU/L (200 IU/L if liver metastases are present) 6)ALT <= 100 IU/L (200 IU/L if liver metastases are present) 7)Serum creatinine <= 1.5 mg/dL 8)PT-INR < 1.5 (< 3.0 for patients treated with oral warfarin) 9)Satisfies at least one of these conditions (i) Urine protein (dip stick method) <= 1+ (ii) UPC (urine protein creatinine) ratio <= 1.0 (iii) Urinary protein <= 1000mg/ 24hours (9)ECOG performance status (PS) of 0 or 1 (10)Life expectancy of >= 3 months (90 days) after enrollment
Key exclusion criteria	(1)Radiotherapy received within 4 weeks (28 days) prior to enrollment (2)Known brain metastasis or strongly suspected of brain metastasis (3)Synchronous cancers or metachronous cancers with a disease-free period of ; 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection. (4)Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.) (5)Patients who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy (6)Nonhealing surgical wound (excluding implanted venous reservoirs) (7)Active hemorrhage requiring blood transfusion (8)Disease requiring systemic steroids for treatment (excluding topical steroids) (9)The patient who has placed colonic stent (10)Intestinal resection within 4 weeks prior to enrollment or colostomy within 2 weeks prior to enrollmentt (11)History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.) (12)patients with unstable angina, myocardial infarction, cerebral hemorrhage, and have a arterial thromboembolism such as cerebral infarction, or history within 24 weeks (168 days) (except for asymptomatic lacunar infarction) (13)Serious drug hypersensitivity (14)Local or systemic active infection requiring treatment, or fever indicating infection (15)NYHA class II or higher heart failure or serious heart disease (16)Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhoea (incapacitating symptoms despite adequate treatment) (17)Poorly controlled hypertension (18)Poorly controlled diabetes mellitus (19)Active hepatitis B (20)Known HIV infection (21)Peripheral neuropathy of; Grade 2 by CTCAE (Japanese edition JCOG version 4.03) (22)Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study
Target sample size	800

Research contact person
Name of lead principal investigator	1st name Kohei Middle name Last name Shitara
Organization	National Cancer Center Hospital East
Division name	Department of Gastrointestinal Oncology
Zip code	277-8577
Address	6-5-1 Kashiwanoha, Kashiwa, Chiba
TEL	04-7133-1111
Email	protocol@paradigm-study.jp

Public contact
Name of contact person	1st name Clinical Trial Information Middle name Last name Contact for Clinical Trial Information
Organization	Takeda Pharmaceutical Company Limited
Division name	Contact for Clinical Trial Information
Zip code	103 - 8668
Address	https://www.takeda.com/jp/who-we-are/contact-us/
TEL	06-6204-2111
Homepage URL
Email	protocol@paradigm-study.jp

Sponsor
Institute	National Cancer Center Hospital East
Institute
Department

Funding Source
Organization	Takeda Pharmaceutical 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	National Cancer Center Hospital East Certified Review Board
Address	6-5-1 Kashiwanoha Kashiwa-shi Chiba,Japan, Chiba
Tel	04-7133-1111
Email	ncche-irb@east.ncc.go.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	JapicCTI-142731
Org. issuing International ID_1	JAPIC
Study ID_2	jRCTs031180246
Org. issuing International ID_2	Japan registry of clinical trials
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 03 Month 23 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	2015 Year 03 Month 20 Day
Date of IRB	2019 Year 01 Month 29 Day
Anticipated trial start date	2015 Year 04 Month 24 Day
Last follow-up date	2021 Year 08 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2015 Year 03 Month 11 Day
Last modified on	2020 Year 05 Month 21 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019460

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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