Panitumumab and RAS, Diagnostically-useful Gene Mutation for mCRC (PARADIGM study)

Phase 3

Completed

• Conditions: Colorectal cancer

• Registration Number: JPRN-jRCT1080222680
• Lead Sponsor: Kohei Shitara

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-05
• Study Completion: 2022-01-14
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: completed
• Sex: All
• Target Recruitment: 823

Inclusion 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 >=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.
*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 >= 1.5*10^3/microL
2)Platelet count >= 1.0*10^4/microL
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

Exclusion 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, non-melanoma 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, arterial thromboembolism such as cerebral infarction, or have history of these desease less than 24 weeks (168 days) before registration (except for lacunar infarction asymptomatic)
(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).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.Overall survival (OS) for All Participants<br>Timeframe: Up to approximately 60 months<br>OS will be measured as the time from the date of randomization to the date of death due to any cause.<br><br>2.OS for Participants with Left-sided Tumors<br>Timeframe: Up to approximately 60 months<br>OS will be measured as the time from the date of randomization to the date of death due to any cause. The left-sided tumors are defined as primary tumors occupying a left-sided site include the descending colon, sigmoid colon, and rectum.