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A phase II trial of TAS-102 in combination with cetuximab for patients with RAS wild-type metastatic colorectal cancer refractory to previous anti-EGFR antibodies

A phase II trial of TAS-102 in combination with cetuximab for metastatic colorectal cancer patients

56

A total of 56 patients were enrolled and analyzed as full analysis set. Of those, median age was 60 (range, 37-77); male/female 33/23; ECOG performance status 0/1 31/25; primary resection yes/no 48/8; number of metastatic sites 0-1/> 2 17/39; best overall response of prior therapy containing anti-epithelial growth factor receptor antibody partial response/stable disease/progression disease 34/12/7.

Between Jun 2017 and Jun 2019, 56 patients were enrolled and treated with the protocol therapy.

The most common grade 3 or worse adverse events were neutropenia (55.4%), white blood cell decreased (35.7 %), anemia (30.4 %), hypomagnesemia (16.1 %), dermatitis acneiform (7.1 %), paronychia (7.1%), appetite loss (7.1 %), dry skin (5.4 %), mucositis (3.6 %), fatigue (1.8 %), and vomiting (1.8 %). There were no deaths during this trail. Most of the severe adverse events was manageable and there was no treatment-related death.

In this study, we set disease control rate (DCR) as the primary endpoint. For sample size calculation, we assumed an improvement of DCR from 45% to 65%. As a result, DCR by independent review was 53.6% (80% confidence interval [CI]: 44.2-62.8%), which did not meet the primary endpoint. ORR was 3.6% (95%CI: 0.4-12.3%). Median PFS was 2.4 months (95% CI: 2.1-3.7 months) and median OS was 9.8 months (95%CI: 7.4-12.2 months).

Among patients with metastatic CRC refractory to prior anti-EGFR antibody antibody, TAS-102 in combination with cetuximab showed manageable safety profiles, but did not improve disease control rate.

Aug. 02, 2022

No

No plan description

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180156

Izawa Naoki

St.Marianna University School of Medicine Hospital

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa

n2izawa@marianna-u.ac.jp

Izawa Naoki

St.Marianna University School of Medicine Hospital

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa

+81-44-977-8111

n2izawa@marianna-u.ac.jp

Complete

June. 20, 2017

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1)histopathologically confirmed unresectable or metastatic colorectal adenocarcinoma
2) Wild-type RAS status
3) Measurable disease by response evaluation criteria in solid tumors (RECIST version 1.1) criteria
4) refractory disease or unable to tolerate agents (fluoropyrimidines, irinotecan, oxaliplatin) and antiangiogenic agent (bevacizumab,ramucirumab and aflibercept), and refractory to anti-EGFR antibodies (cetuximab and panitumumab)
5) No prior TAS-102
6) Patients who have not had major surgery (i.e., thoracotomy or laparotomy) within 4 weeks prior to enrollment.
7) Patients who have not had radiotherapy for bone and/or brain metastases excluding primary colorectal cancer within 2 weeks prior to enrollment
8) Patients who have not had any chemotherapy within 2 weeks prior to enrollment
9) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
10) An estimated life expectancy of at least 12 weeks after enrollment
11) Is able to take medications orally
12) Patients must have the following adequate organ functions
13) Ability to understand and the willingness to sign a written informed consent document

1) Previous severe infusion reaction to Cmab
2) Another malignancy with less than 5 disease-free years
3) Presence of active local or systemic infection under treatment
4) Positive for Hepatitis B surface antigen
5) Radiographic evidence of severe pulmonary fibrosis or interstitial pneumonia on Computed Tomography
6) Symptomatic brain and/or leptomeningeal metastases which needs treatment
7) Serious complications
8) Clinically significant mental or psychological disorder
9) Patients requiring continuous treatment with systemic steroids
10) Females who are pregnant, breastfeeding, or with a positive pregnancy test or males and females of reproductive potential unwilling to use adequate contraception
11) Patients whose participation in the trial was judged to be inappropriate by the attending doctor

Both

Metastatic RAS wild type colorectal cancer with refractory or intolerable to standard chemotherapy

TAS-102 (35 mg/m2/dose) will be administered orally BID on days1-5 and day8-12 every 28 days.
Cmab is administered once a week. The initial dose is 400 mg/m2. The subsequent weekly doses are 250 mg/m2 each.

disease control rate

overall survival, progression free survival, response rate, safety

+81-55-989-5222

Jan. 15, 2019

none