PARADIGM study (PAnitumumab and RAS, DIagnostically-useful Gene Mutation for mCRC)

JRCT ID: jRCTs031180246

Registered date:12/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Colorectal cancer
• Date of first enrollment: 29/05/2015
• Target sample size: 823
• Study type: Interventional
• Intervention(s): Randomization

Outcome(s)

Primary Outcome

The following item concerning all sites and a primary tumor occupying a left-sided site* (hereinafter referred to as "left-side")
Overall survival (OS)
*:Primary tumors occupying a left-sided site include the descending colon, sigmoid colon, and rectum.

Secondary Outcome

Efficacy
The following items concerning all and left-sided sites
Progression free survival (PFS)
Response rate (RR)
Duration of response (DOR)
Percentage of subjects treated with surgical resection after chemotherapy (completer resection) curative resection
Safety
Percentage of subjects with adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

(1)Investigator* and subinvestigator judge a candidate is understand clinical trial and comply this protocol.
*Those who participates in conducting a study and oversight the study duties at a site.
(2)Patients who have given written consent to take part in the study after detailed explanation of the study prior to enrollment.
(3)Aged the above 20to80 under 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 that can be evaluated. It is not essential to be evaluated the tumor according to the RECIST ver. 1.1.
(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/NRAS test will be performed using the in vitro diagnostic listed in the National Health Insurance.
**: Patients with no mutation in any of the codons shown below are considered wild type. It is not considered wild type if either of the codons are not evaluable or not tested.
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/uL
2)Platelet count >= 1.0x104/uL
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

Exclude criteria

(1)Radiotherapy received within 4 weeks (28 days) prior to enrollment. Treatments aimed at relieving pain for bone metastases are excluded.
(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 (esophageal, stomach, and cervical cancer, nonmelanoma skin cancer, bladder cancer, etc.).
(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 less than 24 weeks (168 days) before registration (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 (e.g. Patients who might agree to participate under compulsion).

Related Information

• Primary Sponsor: Shitara Kohei
• Secondary Sponsor: Takeda Pharmaceutical Company Limited
• Secondary ID(s): UMIN000016776/NCT02394795/JapicCTI-142731