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A multicenter, phase II trial to investigate the safety and efficacy of Panitumumab and Irinotecan in Neo Ras Wild type metastatic colorectal cancer patients (C-PROWESS study)

C-PROWESS study (C-PROWESS study)

30

The median age was 66.5 years (interquartile range (IQR) 57-73 years), with 24 patients (80%) having performance status (PS) 0 and six patients (20%) having PS 1. Of the patients, 20 were male (66.7%) and 10 were female (33.3%). Primary tumors were located on the right side in five patients (16.7%) and on the left side in 25 patients (83.3%). A history of primary tumor resection was performed in 27 patients. RAS gene mutation variants included KRAS exon 2 in 24 patients (80%), exon 3 mutation in one patient (3.3%), and other mutations in five patients (16.7%).

The enrolment rate fell below the initial projection at the start of the trial. The key factors contributing to this were the lower-than-anticipated frequency of NeoRAS WT mCRC patients and the greater-than-expected number of patients where enrolment proved difficult due to the treatment being at the salvage line and thus precluding the administration of irinotecan. Consequently, monthly eligibility assessments were conducted, and the importance of the trial was emphasized repeatedly to encourage enrolment. The registration period was extended during protocol revisions in 2023 (one year after commencement) and 2024 (two years after commencement). Progress then proceeded according to the revised registration pace, with registration completed in January 2025 and the final follow-up conducted in October 2025. Of the 31 total registered patients, protocol treatment commenced in all 30 eligible patients, excluding one ineligible patient. The reasons for treatment discontinuation were disease progression in 24 patients (80%), adverse events in four patients (13.3%), and continuation of treatment in two patients (6.7%).

Grade 3 adverse events occurred in 14 patients (46.7%), including skin disorders (4 patients, 13.3%), hypomagnesaemia (3 patients, 10%), diarrhea (3 patients, 10%), appetite loss (3 patients, 10%), and anemia (2 patients, 6.7%). No Grade 4 adverse events were observed, nor were there any treatment-related deaths during the protocol treatment period.

In this trial, the primary endpoint was defined as the response rate. With a threshold response rate of 4% and an expected response rate of 15%, the sample size was calculated based on an alpha level of 0.1, 80% power and a one-year enrolment period. This resulted in a planned enrolment of 30 patients. The median observation period for all enrolled cases was 22.44 months. The response rate was only 6.7% (95% confidence interval: 1.8-16.8), failing to meet the primary endpoint. The secondary efficacy endpoints of median overall and progression-free survival were 16.79 months (95% confidence interval: 12.55-25.46) and 4.11 months (95% confidence interval: 2.99-6.14), respectively.

This study evaluated the efficacy and safety of irinotecan in combination with panitumumab in patients with NeoRAS WT metastatic colorectal cancer. Although the primary endpoint of response rate was not met in the overall population. the 76.7% disease control rate suggests this combination therapy achieved meaningful clinical benefit as a salvage line treatment. the safety findings were consistent with existing reports. There were no treatment-related deaths and tolerability was within acceptable limits.

June. 30, 2026

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210565

Shinozaki Eiji

The Cancer Institute Hospital of JFCR

3-8-31 Ariake, Koto-ku, Tokyo

eiji.shinozaki@jfcr.or.jp

Osumi Hiroki

The Cancer Institute Hospital of JFCR

3-8-31 Ariake, Koto-ku, Tokyo

+81-3-3520-0111

hiroki.osumi@jfcr.or.jp

Complete

Jan. 20, 2022

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

Patients eligible for inclusion in this study have to meet all of the following criteria:
1) Must give written Informed Consent
2) Histologically proven diagnosis of colorectal adenocarcinoma
3) Advanced or recurrent colorectal cancer (excluding appendix and anal canal cancer)
4) Age>= 20 years
5) Eastern Cooperative Oncology Group (ECOG) performance status <= 2
6) At least one measurable lesion according to RECIST version 1.1 criteria evaluated by CT or MRI within 28 days before registration
7) RAS mutation (MT) (KRAS/NRAS exon 2, 3, or 4 MT) confirmed by tumor histology prior to the study enrollment
8) Must have had documentation of the RAS WT confirmed within 28 days from test result date by ctDNA analysis using the OncoBEAM (TM) RAS CRC KIT
9) Must have confirmed refractory or intolerant to previous treatments with chemotherapies including fluoropyrimidines, oxaliplatin, or irinotecan (irinotecan is applied to refractory only), regardless of prior treatment with trifluridine tipiracil hydrochloride, regorafenib, or angiogenesis inhibitors.
10) Life expectancy of at least 60 days
11) Adequate organ functions (bone marrow, liver, renal functions) as defined by the following laboratory values obtained within 14 days prior to the study enrollment:
a.Absolute neutrophil count >= 1500/ mm3
b.Platelets >= 75000/mm3
c.Serum total bilirubin <= 1.5 mg/dL
d.Serum AST(GOT) and ALT(GPT) <= 100 U/L(except for patients with tumor involvement of the liver who must have AST and ALT <= 200 U/L)
e.Serum creatinine <= 1.5 mg/dL

Patients eligible for inclusion in this study must not meet any of the following criteria:
1) Evidence of BRAF V600E MT by tumor histology.
2) Treated with blood transfusion, blood products, or hematopoietic factor products such as Granulocyte Colony Stimulating Factor within 7 days prior to enrollment in this study.
3) Have a history of severe drug hypersensitivity or severe drug allergy
4) Active infection (fever of 38 degree or higher due to infection).
5) Ascites, pleural effusion, or pericardial effusion requiring continuous drainage.
6) Uncontrolled diabetes mellitus.
7) Uncontrolled hypertension.
8) Patients who have been treated with any of the following treatments prior to starting study drug:
a.Extensive surgery <= 4 weeks prior to starting study drug (e.g., surgical treatment with organ resection, excluding colostomy)
b.Proctocolectomy <= 2 weeks prior to starting study drug
c.Any chemotherapy <= 2 weeks prior to starting study drug
d.Radiotherapy <= 2 weeks prior to starting study drug
9) Clinically significant electrocardiographic abnormality or clinically significant cardiovascular accidents within 6 months prior to study enrollment, including myocardial infarction, severe unstable angina, or New York Heart Association functional classification class III or IV congestive heart failure.
10) Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema).
11) History of clinically significant mental disorder or central nervous system disorder.
12) Symptomatic brain metastasis or clinically suspected brain metastasis upon symptoms.
13) Diarrhea that interferes with daily life.
14) Intestinal paralysis, intestinal obstruction.
15) Co-existing active malignancies.
16) Pregnant or lactating women; women of childbearing potential or men with women partners of childbearing potential who are unwilling to use a highly effective method of contraception or avoid intercourse during and upon completion of the study. 17) Patients who are judged by the site physician to be inappropriate for this study.
18) Patients who have been treated with EGFR inhibitors prior to starting study drug.

Both

Neo Ras Wild type metastatic colorectal cancer

Combination therapy of panitumumab plus irinotecan: Patients receive panitumumab (intravenous dose of 6 mg/kg) plus intraveous infusion of irinotecan of 150 mg/m2 (body surface area). Treatment cycles are repeated every 2 weeks until disease progression, unacceptable adverse events, or withdrawal of consent.

Response Rate

Overall survival, Progression free survival, Disease control rate, Adverse event

+81-3-3542-2511

Dec. 23, 2021

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