UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000019081
Receipt number R000022059
Scientific Title A phase I/II study of hybrid brachytherapy for locally advanced cervical carcinoma
Date of disclosure of the study information 2015/09/30
Last modified on 2022/07/15 05:37:57

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Basic information

Public title

A phase I/II study of hybrid brachytherapy for locally advanced cervical carcinoma

Acronym

Cervical cancer- Hybrid brachytherapy

Scientific Title

A phase I/II study of hybrid brachytherapy for locally advanced cervical carcinoma

Scientific Title:Acronym

Cervical cancer- Hybrid brachytherapy

Region

Japan


Condition

Condition

Cervical cancer

Classification by specialty

Obstetrics and Gynecology Radiology

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

A phase I, II study evaluating safety and efficacy of hybrid brachytherapy for locally advanced cervical carcinoma

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2


Developmental phase

Phase I,II


Assessment

Primary outcomes

Phase I part:
Rate of acute non-hematologic toxicity greater than grade 3 which is obviously attributed to hybrid brachytherapy

Phase II part:
2-year pelvic relapse-free survival

Key secondary outcomes

Phase I part:
Pelvic relapse-free survival, overall survival, progression-free survival

Phase II part: dose constraint adherence rate of HBT, 2-year overall survival, 2-year progression-free survival, 2-year metastasis-free survival, the rate of acute toxicity, the rate of late toxicity


Base

Study type

Interventional


Study design

Basic design

Single arm

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Historical

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

External beam irradiation, Chemotherapy, Hybrid intracavitary/interstitial brachytherapy

Patient enrollment period: 8 months after permission of the clinical trial for phase I study, 3 months intermittent pause of enrollment after 20 patients registration, 1 year and 1 months
Follow-up period: 2 years after finish of patients enrollment

Extarnal beam irradiation: whole pelvis irradiation (30Gy/15fr or 30.6Gy/17fr) + central shield (20Gy/10fr or 19.8Gy/11fr)
Systemic chemotherapy: weekly CDDP (40mg/m2)
Hybrid intracavitary/interstitial brachytherapy: starts after the initiation of central shiled, 24Gy/4fr

Interventions/Control_2


Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

75 years-old >=

Gender

Female

Key inclusion criteria

Primary registration
1) Pathologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix
2) Age between 20 and 75 years old
3) FIGO stage IB2, IIA2, IIB, IIIA, IIIB, IVA(bladder invasion)
4) Patients for whom primary radiation therapy is planned
5) Tumor width greater than 5 cm assessed by pretreatment image examination
6) ECOG (Zubrod) performance status 0-2
7) No prior radiation therapy, chemotherapy, nor surgery for cervical cancer
8) Patients with sufficient organ function
- neutrophil count greater than 2,000/mm3
- hemoglobin greater than 8g/dL
- platelets greater than 50,000/mm3
- total bilirubin lower than 1.5mg/dL
- AST (GOT) and ALT (GPT) lower than 100 IU/L
-serum creatinine lower than 1.2mg/dL
-creatinine clearance higher than 60mL/min
9) It is possible to stop taking or do not intake any anticoagulant or antiplatelet
10) No prior chemotherapy or no prior abdominopelvic irradiation
11) Patient must provide study-specific informed consent prior to study entry

Secondary registration
1) Primary registration was already done
2) Tumor width greater than 4 cm assessed by pre-HBT image examination
3) ECOG (Zubrod) performance status 0-2
4) Neutrophil greater than 2,000/mm3 and platelet greater than 50,000/mm3

Key exclusion criteria

Primary registration
1) Patients with para-aortic lymph node metastasis.
2) Uncontrollable diabetes mellitus
3) Uncontrollable hypertension
4) Unstable angina pectoris or transmural myocardial infarction within the last 6 months
5) Prior invasive malignancy unless disease free for a minimum of 5 years. For example, carcinoma in situ of the breast, oral cavity, or esophagus are all permissible.
6) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
7) Body temperature greater than 38 degree Celsicus
8) Psychiatric comorbidities or problems hinders enrollment of the study
9) Active ulcerative colitis or Crohn's disease
10) Active systemic lupus erythematosus or scleroderma
11) Allergy to local anesthesia
12) Attending physician believes the patient is not suitable for the study
13) Positive for hepatitis B Surface antigen

Secondary registration
1) Patients with FIGO IIIA and after 30/30.6 Gy of pelvic irradiation, still depth of the vaginal invasion exceeds 5 mm and cannot be handled with intracavitary brachytherapy
2) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
3) Body temperature greater than 38 degree Celsicus

Target sample size

55


Research contact person

Name of lead principal investigator

1st name Jun
Middle name
Last name Itami

Organization

National Cancer Center Hospital

Division name

Department of Radiation Oncology

Zip code

104-0045

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

TEL

03-3542-2511

Email

namuraka@ncc.go.jp


Public contact

Name of contact person

1st name Naoya
Middle name
Last name Murakami

Organization

National Cancer Center Hospital

Division name

Department of Radiation Oncology

Zip code

104-0045

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

TEL

03-3542-2511

Homepage URL


Email

namuraka@ncc.go.jp


Sponsor or person

Institute

National Cancer Center Hospital, Department of Radiation Oncology

Institute

Department

Personal name



Funding Source

Organization

Japan Agency for Medical Research and development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

National Cancer Center Hospital, Support Center

Address

Tsukiji Chuo-ku 5-1-1

Tel

03-3542-2511

Email

CRL_office@ml.res.ncc.go.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

国立研究開発法人国立がん研究センター中央病院(東京都)
東北大学病院(宮城県)
山形大学医学部附属病院(山形県)
群馬大学医学部附属病院(群馬県)
群馬県立がんセンター(群馬県)
筑波大学附属病院(茨城県)
埼玉医科大学国際医療センター(埼玉県)
東京医科歯科大学医学部附属病院(東京都)
がん研有明病院(東京都)
千葉大学医学部附属病院(千葉県)
国立研究開発法人放射線医学総合研究所重粒子医科学センター病院(千葉県)
大阪医科大学附属病院(大阪府)
大阪大学医学部附属病院(大阪府)
独立行政法人国立病院機構大阪医療センター(大阪府)
神戸大学医学部附属病院(兵庫県)
京都府立医科大学附属病院(京都府)
兵庫県立がんセンター(兵庫県)
川崎医科大学付属病院(岡山県)
香川県立中央病院(香川県)
徳島大学病院(徳島県)
高知大学医学部附属病院(高知県)
独立行政法人国立病院機構福山医療センター(広島県)
九州大学病院(福岡県)
独立行政法人国立病院機構九州がんセンター(福岡県)
日本私立学校振興・共済事業団 東京臨海病院(東京都)
東京都立墨東病院(東京都)
トヨタ記念病院(愛知県)
順天堂大学医学部附属浦安病院(千葉県)

National Cancer Center Hospital, Tokyo
Tohoku University Hospital, Miyagi
Yamagata University Hospital, Yamagata
Gunma University Hospital, Gunma
Gunma Prefectural Cancer Center, Gunma
University of Tsukuba Hospital, Ibaraki
Saitama Medical University International Medical Center, Saitama
Medical Hospital, Tokyo Medical and Dental University, Tokyo
Cancer Institute Hospital, Tokyo
Chiba University Hospital, Chiba
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba
Osaka Medical College Hospital, Osaka
Osaka University Hospital, Osaka
National Hospital Organization Osaka National Hospital, Osaka
Kobe University Hospital, Hyogo
University Hospital, Kyoto Prefectural University of Medicine, Kyoto
Hyogo Cancer Center, Hyogo
Kawasaki Medical School Hospital, Okayama
Kagawa Prefectural Central Hospital, Kagawa
Tokushima University Hospital, Tokushima
Kochi Medical School Hospital, Kochi
National Hospital Organization Fukuyama Medical Center, Hiroshima
Kyushu University Hospital, Fukuoka
National Hospital Organization Kyushu Cancer Center, Fukuoka
Tokyo Rinkai Hospital, Tokyo
Tokyo Metropolitan Bokutoh Hospital, Tokyo
Toyota Memorial Hospital, Aichi
Juntendo University Urayasu Hospital, Chiba


Other administrative information

Date of disclosure of the study information

2015 Year 09 Month 30 Day


Related information

URL releasing protocol


Publication of results

Partially published


Result

URL related to results and publications

https://doi.org/10.1093/jjco/hyac072

Number of participants that the trial has enrolled

52

Results

The lower range of 90% CI of 2-year PPFS was 69.7% was higher than the historical control, therefore, the primary endpoint of this study was met and it can be said that HBT is superior to conventional ICBT in terms of local control based on a prospective clinical trial. In addition, the primary endpoint of phase I part of this study was the rate of acute non-hematologic adverse events related to HBT lower than 10% and it was shown that it was < 10% and feasibility of HBT was demonstrated with this study.

Results date posted

2022 Year 07 Month 15 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

BetweenOctober2015andOctober2019,74patientsunderwentprimaryregistration,with52patientseventuallyproceedingtothesecondaryregistration.Themedianpretreatmenttumorwidthwas5.7cm,andFIGOStageswereIB210,IIA22,IIB20andIIIB20,respectively.

Participant flow

Patient accrual was slower than the initially expected period of two years, and although the total accrual number was fewer than the initially intended number of 55, it was decided that further prolongation of patient accrual was inappropriate, patient accrual was stopped when the total patient number exceeded 50. When the 20th patient proceeded to the secondary registration, patient accrual was temporarily stopped to see whether grade 3 or higher acute non-hematological adverse events related to the hybrid of intracavitary and interstitial brachytherapy (HBT) was lower than 10%. Because it was lower than 10%, the clinical study proceeded to the phase II part. All patients completed the planned protocol treatment, and late severe adverse events related to the protocol treatment were within what was initially expected.

Adverse events

Late grade 3 or higher non-hematologic adverse events were observed in three patients (5.8%) and one grade 4 event was observed only in one patient (1.9%, uterine bleeding). No grade 5 adverse event was observed.

Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

No longer recruiting

Date of protocol fixation

2015 Year 07 Month 19 Day

Date of IRB

2015 Year 07 Month 28 Day

Anticipated trial start date

2015 Year 10 Month 01 Day

Last follow-up date

2021 Year 11 Month 01 Day

Date of closure to data entry

2022 Year 04 Month 14 Day

Date trial data considered complete

2022 Year 04 Month 14 Day

Date analysis concluded

2022 Year 04 Month 14 Day


Other

Other related information



Management information

Registered date

2015 Year 09 Month 20 Day

Last modified on

2022 Year 07 Month 15 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022059


Research Plan
Registered date File name
2017/09/24 HBTプロトコール 17版.docx

Research case data specifications
Registered date File name

Research case data
Registered date File name