UMIN-CTR Clinical Trial

Public title

A Randomized Phase III Trial of Adjuvant Chemotherapy with UFT following Curative Radiation Therapy for Locally Advanced Cervical Cancer

Acronym

A Randomized Trial of Adjuvant Chemotherapy with UFT following Curative Therapy for Locally Advanced Cervical Cancer

Scientific Title

A Randomized Phase III Trial of Adjuvant Chemotherapy with UFT following Curative Radiation Therapy for Locally Advanced Cervical Cancer

Scientific Title:Acronym

A Randomized Trial of Adjuvant Chemotherapy with UFT following Curative Therapy for Locally Advanced Cervical Cancer

Region

Japan

Condition

Stage Ib2-IVa cervical cancer with Curative Radiation Therapy

Classification by specialty

Obstetrics and Gynecology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Usefulness of Adjuvant Chemotherapy with UFT following Curative Therapy for patients with StageIb2-IVa cervical cancer

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

Progression-free survival

Key secondary outcomes

Overall Suvival/Adverse event/Quality of Life/Cost effectiveness

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Open -no one is blinded

Control

No treatment

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Observation

Interventions/Control_2

UFT 300 or 400mg/Day

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

75

years-old

>=

Gender

Female

Key inclusion criteria

1)Pathologicaly confirmed cervical cancer(squamous cell carcinoma,adenosquamous carcinoma,adenocarcinoma)
2)FIGO: Ib2, IIa, IIb, IIIa, IIIb, IVa
3)Patients who have received CCRT within 3-12 weeks and determined to be PR or CR by CT or MRI.
4)Age: 20 years old-75 years old
5)Performance status: ECOG 0-2
6)Adequate organ functions.
7)Patients who have signed to an approved informed consent.

Key exclusion criteria

1)Patients who have received hysterectomy after radiation therapy.
2)Patients with uterine stump cancer.
3)Patients who have received NAC.
4)Patients with active infection.
5)Patients who have myocardial infarction or unstable angina or uncontrolled arrhythmia within 6 months.
6)Patients with severe complications (uncontrolled hypertension,uncontrolled diabetes,bleeding tendency,or rheumatology).
7)Patients who have had any other cancer within the past 5 years.
8)Patients with watery diarrhea.
9)Patients with psychiatric disease.
10)Patients who are pregnant or breast feeding.
11)Patients who have a history of hypersensitivity to UFT
12)Patients who are considered to be inappropriate for this study judged by the treating physician

Target sample size

350

Name of lead principal investigator

1st name	Keiichi
Middle name
Last name	Fujiwara

Organization

Saitama Medical University International Medical Center

Division name

Gynecologic Oncology

Zip code

350-1298

Address

1397-1 Yamane,Hidaka-City Saitama

TEL

042-984-4111

Email

fujawara@saitama-med.ac.jp

Name of contact person

1st name	Keiichi
Middle name
Last name	Fujiwara

Organization

GOTIC002 Coordinating Office

Division name

Saitama Medical University International Medical Center

Zip code

350-1298

Address

1397-1 Yamane,Hidaka-City Saitama

TEL

042-984-4111

Homepage URL

Email

fujawara@saitama-med.ac.jp

Institute

Gynecologic Oncology Trial and Investigation Consortium

Institute

Department

Personal name

Organization

Gynecologic Oncology Trial and Investigation Consortium

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Saitama Medical University Certified Review Board

Address

1397-1, Yamane, Hidaka-City, Saitama-Pref, Japan

Tel

042-984-4122

Email

tokutei@saitama-med.ac.jp

Secondary IDs

YES

Study ID_1

jRCTs031180244

Org. issuing International ID_1

Japan Registry of Clinical Trials(jRCT)

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

埼玉医科大学国際医療センター（埼玉県）、
鳥取大学医学部附属病院（鳥取県）、
久留米大学病院（福岡県）、
埼玉医科大学総合医療センター（埼玉県）、
埼玉県立がんセンター（埼玉県）、
筑波大学附属病院（茨城県）、
獨協医科大学病院（栃木県）、
自治医科大学附属病院（栃木県）、
群馬大学医学部附属病院（群馬県）、
立正佼成会附属佼成病院（東京都）、
群馬県立がんセンター（群馬県）、
鳥取市立病院（鳥取県）、
九州大学病院（福岡県）、
四国がんセンター（愛媛県）、
順天堂大学医学部附属順天堂医院（東京都）、
徳島大学病院（徳島県）、
広島市立広島市民病院（広島県）、
県立広島病院（広島県）、
東京慈恵会医科大学附属病院（東京都）、
高崎総合医療センター（群馬県）、
聖マリアンナ医科大学病院（神奈川県）、
東京医科歯科大学医学部附属病院（東京都）、
千葉大学医学部附属病院（千葉県）、
大阪大学医学部附属病院（大阪府）、
愛媛大学医学部附属病院（愛媛県）、
東京慈恵会医科大学附属第三病院（東京都）、
杏林大学医学部附属病院（東京都）、
鹿児島大学病院（鹿児島県）、
北海道大学病院（北海道）、
琉球大学病院（沖縄県）、
東京慈恵会医科大学附属柏病院（千葉県）、
兵庫県立がんセンター（兵庫県）、
香川県立中央病院（香川県）、
鹿児島医療センター（鹿児島県）、
聖マリア病院（福岡県）、
茨城県立中央病院（茨城県）、
熊本大学医学部附属病院（熊本県）、
北里大学病院（神奈川県）、
聖隷浜松病院（静岡県）、
旭川医科大学病院（北海道）、
三重大学医学部附属病院（三重県）、
岩手医科大学附属病院（岩手県）、
東京医科大学病院（東京都）

Date of disclosure of the study information

2010

Year

05

Month

24

Day

URL releasing protocol

https://jrct.mhlw.go.jp/latest-detail/jRCTs031180174

Publication of results

Published

URL related to results and publications

https://doi.org/10.1016/j.ejca.2025.115304

Number of participants that the trial has enrolled

351

Results

A phase III randomized study was conducted to evaluate whether 2 years of maintenance therapy with UFT after curative CCRT improves prognosis in patients with locally advanced Stage Ib2 to IVa cervical cancer. Results was not able to demonstrate that neither progression-free survival (PFS) nor overall survival (OS) was prolonged. Adverse events that occurred during the study period were, not surprisingly, more common in the Arm UFT, but most were minor (Grade 2 or less).

Results date posted

2025

Year

06

Month

16

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2025

Year

02

Month

15

Day

Baseline Characteristics

The background factors of 178 patients in the follow-up group (Arm O) and 173 patients in the adjuvant chemotherapy group (Arm UFT) were as follows.
Age (mean+/-SD) was 52.9+/-12.5 years for Arm O and 53.8+/-11.6 years for Arm UFT.
FIGO staging was most common in stage IIb, Arm O: 43.8%, Arm UFT: 45.7%, followed by stage IIIb Arm O: 34.8%, Arm UFT: 32.4%.
The histological type was mostly squamous cell carcinoma (Arm O: 90.4%, Arm UFT: 89.0%).
PS was good in most cases (Arm O: 97.8%, Arm UFT: 94.8%).
The chemotherapeutic agent used in combination with prior concurrent chemoradiotherapy radiation therapy (CCRT) was cisplatin in most cases (Arm O: 94.9%, Arm UFT: 95.4%).
The status of cervical lesions at the time of enrollment in the study after CCRT was tumor-free in the majority of patients (Arm O: 83.1%, Arm UFT: 82.1%).
There were no significant differences in these background factors between the two groups.

Participant flow

The pace of enrollment was slower than originally projected, so the protocol was amended three times (January 15, 2013, August 11, 2015, and October 19, 2016). The original plan was to accumulate 530 cases over 3 years of enrollment and a total study period of 6 years, but was eventually revised to 9 years of enrollment and 12 years of total study period, with a target number of 350 cases. In fact, 351 patients were enrolled, 178 were assigned to Arm O and 173 to Arm UFT, and these were the target population for the efficacy analysis. For the safety evaluation, 176 of the Arm O patients (excluding 2 patients who discontinued before the start of observation) and 168 of the Arm UFT patients (excluding 5 patients who discontinued before the start of UFT administration) were included in the analysis population.

Adverse events

No treatment-related deaths occurred.

For all adverse events (AEs), all Grade occurred significantly more frequently in Arm UFT: 93.5% than in Arm O: 73.9% (Odds Ratio (Arm UFT/Arm O) = 5.05 (95%CI: 2.51, 10.15)).
Grade 3 or higher AEs also occurred more frequently in Arm UFT: 22.6% than in Arm O: 15.9%.
We assume that the reason why AEs also occurred in Arm O was due to concurrent chemoradiotherapy (CCRT) administered prior to case enrollment.
On the other hand, the breakdown of AEs in Arm UFT showed that anemia, gastrointestinal symptoms, abnormal laboratory values, and electrolyte abnormalities were the most common AEs. AEs of Grade 3 or higher included neutropenia in 9 patients (5.4%), leukopenia in 8 patients (4.8%), anemia in 6 patients (3.6%), diarrhea in 3 patients (1.8%), and increased ALT in 3 patients (1.8%). Thrombosis occurred in a small number of cases, 1 (0.6%) in Arm O and 2 (1.2%) in Arm UFT, with the Arm O case being Grade 2 and the Arm UFT case being Grade 3, both reported as SAE.


Among the 168 patients treated with UFT, causally related adverse events occurred in 142 (84.5%). Of these, 30 (17.9%) were Grade 3 or higher, and the most common adverse events were neutropenia in 9 (5.4%), leukopenia in 8 (4.8%), anemia in 4 (2.4%), increased ALT in 3 (1.8%), diarrhea in 3 (1.8%), and fatigue in 2 (1.2%).

SAE was reported in 9 (5.1%) patients in Arm O and 8 (4.8%) patients in Arm UFT.
Arm O: 1 case of anemia, 2 cases of intestinal obstruction, 1 death of unknown cause, 2 cases of peritonitis, 1 case of infectious enteritis, 1 case of radiation enteritis, and 1 case of hypokalemia.
In Arm UFT, 1 case of rectal fistula, 1 case of rectal bleeding, 1 case of pain, 1 case of fracture, 1 case of hematuria, and 4 cases of thrombosis were reported. Except for the thrombosis, the other cases suggest the possibility of SAE associated with radiation therapy.

Outcome measures

Primary endpoint
Progression-Free Survival (PFS), showed a 5-year PFS rate of 61.3% (90% CI: 54.8-67.1) for Arm O and 62.0% (90% CI: 55.4-67.8) for Arm UFT with a hazard ratio (HR) of 0.92 (90%CI: 0.69-1.22). The p-value was 0.634, with no difference between the two groups.

Secondary Endpoints
Overall Survival (OS) results showed that the 5-year OS rate was 77.6% (90%CI: 71.8-82.4) for Arm O and 76.1% (90%CI: 70.1-81.1) for Arm UFT, with a hazard ratio of 1.04 (90%CI: 0.73-1.47), p=0.869. There was no difference between the two groups.

Subgroup Analysis
In the subgroup analysis of PFS and OS, there was no difference between the two groups in FIGO (=<II, >=III), age (<65 years, >=65 years), and PS (0, 1).

The odds ratio Arm UFT/Arm O of adverse event occurrence was 5.05 (95% CI: 2.51, 10.15), and, not surprisingly, was more common in Arm UFT than in Arm O. However, there was no difference in the incidence of SAE, 5.1% for Arm O and 4.8% for Arm UFT, and most of the adverse events that occurred with UFT administration were minor.
Quality of life is currently under analysis.
Cost-effectiveness will be analyzed in the future.

Plan to share IPD

No

IPD sharing Plan description

No

Recruitment status

Main results already published

Date of protocol fixation

2010

Year

04

Month

26

Day

Date of IRB

2010

Year

05

Month

12

Day

Anticipated trial start date

2010

Year

05

Month

21

Day

Last follow-up date

2021

Year

10

Month

31

Day

Date of closure to data entry

2022

Year

02

Month

28

Day

Date trial data considered complete

2022

Year

03

Month

14

Day

Date analysis concluded

2022

Year

08

Month

09

Day

Other related information

Registered date

2010

Year

05

Month

21

Day

Last modified on

2025

Year

06

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004420