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Panitumumab re-challenge strategy for liquid RAS mutation negative metastatic colorectal cancer

Phase 2
Conditions
RAS/BRAF V600E wild-type unresectable metastatic colorectal cancer
Registration Number
JPRN-jRCTs031190096
Lead Sponsor
Ohta Takashi
Brief Summary

The efficacy of panitumumab + irinotecan therapy as an anti-EGFR antibody rechallenge was insufficient for colorectal cancer patients who were determined to be negative for blood RAS mutations by ctDNA analysis. In the future, it was considered necessary to examine effect predictors to increase efficacy.

Detailed Description

Not available

Recruitment & Eligibility

Status
Complete
Sex
All
Target Recruitment
50
Inclusion Criteria

1)Histological diagnosis of primary colorectal adenocarcinoma.
2)RAS(KRAS/NRAS)and BRAF V600E wild type analyzed by tumor tissue.
3)Intolerant or refractory to chemotherapy including a fluoropyrimidine, oxaliplatin and irinotecan.
4)Complete or partial response to previous chemotherapy including anti-EGFR antibody (cetuximab or panitumumab).
5)Documentation of progression to previous anti-EGFR antibody within 2 months after last anti-EGFR antibody administration.
6)Negative for plasma RAS mutant within 28 days before registration.
7)Time between the end of previous anti-EGFR antibody and the start of protocol treatment with panitumumab plus irinotecan >= 4 months.
8)Measurable disease according to RECIST guideline v1.1.
9)ECOG 0 or 1.
10)Age >= 20 year old.
11)Adequate major organ function assessed within 14 days before registration.
12)Life expectancy of at least 12 weeks.
13)Written informed consent obtained.

Exclusion Criteria

1)Severe comorbidity.
2)Underwent one of following treatments before protocol treatment;
a. Extensive surgery within 4 weeks.
b. Colostomy/ileostomy within 2 weeks.
c. Chemotherapy within 2 weeks.
d. Radiation therapy within 2 weeks.
3)CTCAE Grade >= 2 adverse events due to previous therapy, which are not recovered.
4)History of severe infusion reactions to anti-EGFR antibody.
5)Intolerant to previous irinotecan therapy.
6)Comorbidity or history of severe pulmonary disease.
7)Men/women who are unwilling to avoid pregnancy. Women who are pregnant or breastfeeding. Women with a positive pregnancy test.
8)Active HCV or HIV infection.
9)Any other patients who are regarded as inadequate for study enrollment by investigators.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Objective response rate:ORR<br>(Investigator's judgment based on RECIST guideline ver. 1.1)
Secondary Outcome Measures
NameTimeMethod
Progression free survival:PFS<br>Time to treatment failure:TTF<br>Duration of response:DoR<br>Overall survival:OS<br>Disease control rate:DCR<br>Rate of adverse events <br>ORR, PFS, TTF, DoR, OS, DCR depending on presence or absence of each gene abnormality in ctDNA analysis at the time of discontinuation of administration before and during anti-EGFR antibody rechallenge
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