UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000016776 |
|---|---|
| Receipt number | R000019460 |
| 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 |
| Date of disclosure of the study information | 2015/03/23 |
| Last modified on | 2024/03/18 10:04:23 |
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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
Japan.ONC.Evidence.Gen@takeda.com
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
Japan.ONC.Evidence.Gen@takeda.com
Sponsor or person
Institute
National Cancer Center Hospital East
Institute
Department
Personal name
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
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
https://jamanetwork.com/journals/jama/fullarticle/2803803
Publication of results
Published
Result
URL related to results and publications
https://jamanetwork.com/journals/jama/fullarticle/2803803
Number of participants that the trial has enrolled
823
Results
For the efficacy, mFOLFOX6 + panitumumab demonstrated a statistically significant improvement in OS, the primary endpoint, as compared to mFOLFOX6 + bevacizumab in patients with RAS wild-type, left-sided metastatic colorectal cancer for both primary tumors occupying left-sided and overall.The safety profile of panitumumab was similar to what has already been reported without newly reported safety concerns.
Results date posted
| 2023 | Year | 01 | Month | 20 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2023 | Year | 04 | Month | 19 | Day |
Baseline Characteristics
Please refer the manuscript;
https://jamanetwork.com/journals/jama/fullarticle/2803803
Participant flow
Please refer the manuscript;
https://jamanetwork.com/journals/jama/fullarticle/2803803
Adverse events
Please refer the manuscript;
https://jamanetwork.com/journals/jama/fullarticle/2803803
Outcome measures
Please refer the manuscript;
https://jamanetwork.com/journals/jama/fullarticle/2803803
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
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
| 2022 | Year | 02 | Month | 04 | Day |
Date of closure to data entry
| 2022 | Year | 02 | Month | 04 | Day |
Date trial data considered complete
| 2022 | Year | 02 | Month | 10 | Day |
Date analysis concluded
| 2022 | Year | 03 | Month | 31 | Day |
Other
Other related information
Management information
Registered date
| 2015 | Year | 03 | Month | 11 | Day |
Last modified on
| 2024 | Year | 03 | Month | 18 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019460
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