UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000017242
Receipt number R000019997
Scientific Title Effectiveness of Adjuvant Intermittent Endocrine Therapy Following Neoadjuvant Endocrine Therapy and External Beam Radiation Therapy in Men With Locally Advanced Prostate Cancer
Date of disclosure of the study information 2015/05/01
Last modified on 2020/10/29 17:51:40

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Basic information

Public title

Effectiveness of Adjuvant Intermittent Endocrine Therapy Following Neoadjuvant Endocrine Therapy and External Beam Radiation Therapy in Men With Locally Advanced Prostate Cancer

Acronym

RCT on the Effectiveness of Intermittent Hormonal Therapy After EBRT

Scientific Title

Effectiveness of Adjuvant Intermittent Endocrine Therapy Following Neoadjuvant Endocrine Therapy and External Beam Radiation Therapy in Men With Locally Advanced Prostate Cancer

Scientific Title:Acronym

RCT on the Effectiveness of Intermittent Hormonal Therapy After EBRT

Region

Japan


Condition

Condition

prostate cancer

Classification by specialty

Urology Radiology

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer.

Basic objectives2

Others

Basic objectives -Others

The present assessment of combination therapy with EBRT and endocrine therapy for locally advanced prostate cancer may be of positive concern. However, it may be difficult to answer how long neoadjuvant and/ or adjuvant endocrine therapy should be used. There have been no RCTs comparing the treatment efficacy and QOL between long-term adjuvant endocrine therapy and intermittent adjuvant endocrine therapy after treatment with EBRT and neoadjuvant endocrine therapy for locally advanced prostate cancer. To answer uncertainties on the above issues, the present multi-center RCT was conducted as a national cancer research project, which has been supported by the Ministry of Health, Labor and Welfare in Japan.

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III


Assessment

Primary outcomes

biochemical relapse-free survival

Key secondary outcomes

overall survival, cancer-specific survival and longitudinal QOL assessment


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

LHRH-agonist is injected all participants until 6 months after completing EBRT every 4 weeks or 3 months according to the drug information.
Adjuvant long-term androgen deprivation therapy (ADT) group: ADT following to EBRT continue for 5 years in total (including neoadjuvant and concomitant ADT)

Interventions/Control_2

Adjuvant intermittent androgen deprivation therapy (ADT) group: ADT must be stopped 6 months after the day of final EBRT treatment. Then, stop or start to ADT according to the protocol during intermittent ADT stage

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


Not applicable

Age-upper limit

79 years-old >=

Gender

Male

Key inclusion criteria

1)Pathologically confirmed prostate cancer
2)Clinical stage is T3N0M0 or T4N0M0 (bladder neck invasion only)
3)Untreated prostate cancer
4)Performance status is 0 or 1
5)Aged younger than 80 years
6)Laboratory data is fit the following criteria within 14 days before the registration
a)White blood cell is 3.0X103/ul or higher, Hemoglobin levels is 10.0g/dl or higher and Platelet is 10X10000/ul or higher
b) Serum creatinine levels is 2.0 mg/dl or lower, GOT is 100 U/L or lower, GPT is 100 U/L or lower
7) Restriction of concomitant medication and treatment
a) No history of undergoing prostate surgery for benign prostatic hyperplasia, which includes transurethral resection of the prostate (TUR-P), subcapsular prostatectomy, or other operation or thermotherapy to the prostate.
b) No medication of adrenocortical steroid agent
c) No medication of antiandrogen for benign prostatic hyperplasia
8) Written informed consent must be done and get agreement on the enrollment of the present study by participants

Key exclusion criteria

1) Having uncontrolled other malignancy
2) Having uncontrolled hypertension (Diastolic blood pressure 120mmHg or higher)
3) Having severe disease in brain or central nerve system
4) Having collagen disease
5) Having uncontrolled diabetes mellitus
6) Having any other problem that researchers judge unfit for the present study

Target sample size

300


Research contact person

Name of lead principal investigator

1st name Kazuto
Middle name
Last name Ito

Organization

Gunma University

Division name

Urology

Zip code

3718511

Address

3-39-22, Showa-machi, Maebashi, Gunma, 3718511, Japan

TEL

0272208306

Email

kzito@gunma-u.ac.jp


Public contact

Name of contact person

1st name Atsuko
Middle name
Last name Ohyama

Organization

Gunma University

Division name

Urology

Zip code

3718511

Address

3-39-22, Showa-machi, Maebashi, Gunma, 3718511, Japan

TEL

0272208303

Homepage URL


Email

a-ohyama@gunma-u.ac.jp


Sponsor or person

Institute

Department of Hygiene and Preventive Medicine, School of Health Sciences and Nursing, University of Tokyo

Institute

Department

Personal name



Funding Source

Organization

the Ministry of Health, Labor
and Welfare in Japan

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization



Other related organizations

Co-sponsor

National Cancer Center Hospital
Sapporo Medical University School of Medicine
The Cancer Institute Hospital of JFCR
Graduate School of Medical Sciences, Kyushu University
Osaka Medical Center for Cancer and Cardiovascular Diseases
Tokyo Metropolitan Cancer and Infections disease Center Komagome Hospital
Koshigaya Hospital, Dokkyo Medical University
Kitazato University Hospital
Tokyo Medical Center
Shikoku Cancer Center
Ibaraki Prefectural Central Hospital and Cancer Center
Gunma Prefectual Cancer Center
Isesaki Municipal Hospital
Miyagi Cancer Center

Name of secondary funder(s)

National Cancer Center Hospital


IRB Contact (For public release)

Organization

Clinical Investigation and Research Unit

Address

3-39-15, Showa-machi, Maebashi, Gunma, 3718511, Japan

Tel

027-220-8740

Email

gunmaciru-office@umin.ac.jp


Secondary IDs

Secondary IDs

YES

Study ID_1

12-14

Org. issuing International ID_1

The Ministry of Health, Labor and Welfare in Japan

Study ID_2

15-2

Org. issuing International ID_2

The Ministry of Health, Labor and Welfare in Japan

IND to MHLW



Institutions

Institutions

群馬大学病院(群馬県)、国立がん研究センター中央病院(東京都)、札幌医科大学医学部(北海道)、がん研有明病院(東京都)、九州大学大学院医学研究院(福岡県)、大阪府立成人病センター(大阪府)、がん・感染症センター都立駒込病院(東京都)、獨協医科大学越谷病院(埼玉県)、北里大学医学部(神奈川県)、東京医療センター(東京都)、四国がんセンター(愛媛県)、茨城県立中央病院(茨城県)、群馬県立がんセンター(群馬県)、伊勢崎市民病院(群馬県)、宮城県立がんセンター(宮城県)


Other administrative information

Date of disclosure of the study information

2015 Year 05 Month 01 Day


Related information

URL releasing protocol

http://onlinelibrary.wiley.com/doi/10.1002/pros.20171/abstract

Publication of results

Published


Result

URL related to results and publications

https://upload.umin.ac.jp/cgi-bin/icdr/ctr_up_reg_f5.cgi

Number of participants that the trial has enrolled

303

Results

Median follow-up duration after randomization was 8.2 years. Arms 1 and 2 enrolled 136 and 144 patients, respectively. Of them, 24 and 30 had biochemical progression, and five and six died due to prostate cancer, respectively. The 5-year bRFS rates were 84.8% and 82.8% in arm 1 and arm 2, respectively (hazard ratio [HR], 1.132; 95%CI, 0.744-1.722). Non-inferiority of intermittent ADT against continuous ADT was not confirmed statistically.

Results date posted

2019 Year 04 Month 25 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2020 Year 06 Month 23 Day

Baseline Characteristics

Patients with locally advanced prostate cancer

Participant flow

Patients with locally advanced prostate cancer were randomized after 6 months of induction by ADT if the prostate-specific antigen level was <10 ng/mL. A total of 280 participants were divided randomly into two arms between 2000 and 2006. All participants underwent 72-Gy EBRT combined with 2 months of concomitant and 6 months of adjuvant ADT. Thereafter, the patients were treated with 5 years of continuous ADT (arm 1) or intermittent ADT (arm 2).

Adverse events

There was no grade 3 or worse adverse events in the study

Outcome measures

The definition of PSA recurrence was the modified Phoenix definition, which is the PSA nadir + 2 ng/mL during the on-phase of ADT. PSA relapse was defined as tumor progression to castration registrant status. Clinical relapse was defined as progressive disease at a new site, local progression, worsening performance status, or body weight loss due to progression of prostate cancer regardless of ADT status.
The primary endpoint at the start of the trial was the biochemical relapse-free rate (bRFR). However, most clinical trials have been used biochemical relapse-free survival (bRFS), which is defined events as the last date of PSA relapse or any clinical relapse if it occurs earlier than the PSA relapse, or any cause of death. Therefore, bRFS was used as a primary endpoint in the final analysis. The secondary endpoints were overall survival (OS), CSS, and a QOL assessment.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2000 Year 10 Month 01 Day

Date of IRB

2000 Year 11 Month 28 Day

Anticipated trial start date

2001 Year 01 Month 01 Day

Last follow-up date

2013 Year 03 Month 31 Day

Date of closure to data entry

2014 Year 03 Month 31 Day

Date trial data considered complete

2015 Year 03 Month 31 Day

Date analysis concluded

2016 Year 03 Month 31 Day


Other

Other related information



Management information

Registered date

2015 Year 04 Month 22 Day

Last modified on

2020 Year 10 Month 29 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019997


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name