Observation or Radical Treatment in Patients With Prostate Cancer

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00499174
• Collaborator: National Cancer Institute (NCI) (NIH), Cancer and Leukemia Group B (Other), Eastern Cooperative Oncology Group (Other), Southwest Oncology Group (Other), Radiation Therapy Oncology Group (Other), Institute of Cancer Research, United Kingdom (Other)
• Enrollment: 180
• Locations: 13
• Arms: 2
• Actual Duration (Months): 66.9
• Patients Per Site: 13.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Sometimes prostate tumours may not need treatment until they progress. In this case, observation may be sufficient. Radical treatments, such as radical prostatectomy or radiation therapy, may be effective in treating prostate cancer when it is first diagnosed. It is not yet known whether active surveillance is more effective than radical treatment as an initial intervention in favorable prognosis prostate cancer.

PURPOSE: This randomized phase III trial is studying active surveillance to see how well it works compared with radical treatment as an initial intervention in patients with favorable prognosis prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Procedure: conventional surgery; Radiation: brachytherapy; Radiation: external beam radiation therapy; Procedure: Biopsies	N/A

Detailed Description

OBJECTIVES:

Primary

• To compare disease-specific survival of patients with favorable risk prostate cancer treated with radical prostatectomy or radical radiotherapy at the time of initial diagnosis vs active surveillance and selective intervention based on pre-specified biochemical, histological, or clinical progression criteria.

Secondary

• To compare overall survival, quality of life using the EPIC-26, RAND SF-12, and State-Trait Anxiety Inventory, distant disease-free survival, PSA relapse/progression after radical intervention, and initiation of androgen deprivation therapy between the two treatment arms.

• To determine the proportion of patients on the active surveillance arm who receive radical intervention for prostate cancer.

• To determine if PSA doubling-time prior to diagnosis predicts eventual outcome.

• To determine if molecular biomarkers predict outcome.

OUTLINE: This is a prospective, randomized, multicenter study. Patients are stratified by treatment center, ECOG performance status (0 vs 1 or 2), disease stage (T1 vs T2), baseline PSA value (ng/mL or μg/L) (< 5.0 vs ≥ 5.0 and ≤ 10.0), and age (< 65 years vs ≥ 65 years). Patients are randomized to 1 of 2 arms.

• Arm I: Patients undergo radical intervention (radical prostatectomy or radiotherapy [external-beam radiotherapy 5 days a week for 4-8 weeks; permanent prostate brachytherapy; or high-dose rate temporary brachytherapy], based on patient and physician preference).

• Arm II: Patients undergo active surveillance with radical intervention at the time one or more pre-specified criteria (biochemical progression, histologic/grade progression, and/or clinical progression) are met.

Quality of life is assessed by the EPIC-26, RAND SF-12, and State Anxiety Inventory at baseline, periodically during study treatment, and after completion of radical treatment.

After completion of radical treatment, patients are followed every 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed With Favourable Risk Prostate Cancer [START]
• Actual Study Start Date: Jun 15, 2007
• Actual Primary Completion Date: Dec 31, 2011
• Actual Study Completion Date: Jan 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Active Surveillance Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression
Active Comparator: Radical Intervention Radical prostatectomy or radiotherapy based on patient and physician preference	Procedure: conventional surgery; Radical prostatectomy; Radiation: brachytherapy; high dose rate temporary seed implant; permanent seed implant.; Radiation: external beam radiation therapy; 3D conformal radiation therapy; intensity modulated radiation therapy.; Procedure: Biopsies; Periodic repeat biopsies

Outcome Measures

Primary Outcome Measures

1. Disease-specific Survival [5 years 6 months]

   Time from the date of randomization to the date of death due to prostate cancer.

Secondary Outcome Measures

1. Overall Survival [5 years 6 months]

   Time from randomization to the date of death due to any causes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Diagnosed within 6 months prior to randomization

• Patient has been classified as favorable risk as defined by the following:

• Clinical stage T1b, T1c, T2a, or T2b at the time of diagnosis

• Clinical (diagnostic biopsy) Gleason score ≤ 6

• PSA ≤ 10.0 ng/mL

• Physical examination, rectal examination, and transrectal ultrasound have been done within 6 months prior to randomization and radiographic studies, if indicated, are negative for metastasis

• Patient is a suitable candidate for radical prostatectomy or radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0, 1, or 2

• Patient has a minimum life expectancy of > 10 years

• In centers participating in the quality of life component of the study, the patient is able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French

• No history of other malignancies, except adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years from study randomization

PRIOR CONCURRENT THERAPY:

• No previous treatment for prostate cancer, including surgery (excluding biopsy and TURP), radiotherapy, or androgen deprivation therapy for greater than 3 months

• No planned androgen therapy except in the context of radical therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Unit at Vancouver Coastal	Vancouver	British Columbia	Canada	V5Z 1M9
2	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
3	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	AIB 3V6
4	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
5	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
6	Ottawa Health Research Institute - General Division	Ottawa	Ontario	Canada	K1H 8L6
7	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
8	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
9	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
10	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
11	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
12	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
13	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1

Sponsors and Collaborators

• NCIC Clinical Trials Group
• National Cancer Institute (NCI)
• Cancer and Leukemia Group B
• Eastern Cooperative Oncology Group
• Southwest Oncology Group
• Radiation Therapy Oncology Group
• Institute of Cancer Research, United Kingdom

Investigators

• Study Chair: Laurence H. Klotz, MD, Toronto Sunnybrook Regional Cancer Centre
• Study Chair: Adam S. Kibel, MD, Washington University Siteman Cancer Center
• Study Chair: Martin G. Sanda, MD, Beth Israel Deaconess Medical Center
• Study Chair: Ian M. Thompson, MD, The University of Texas Health Science Center at San Antonio
• Study Chair: Richard Choo, M.D, Mayo Clinic
• Study Chair: Chris Parker, M.D, Royal Marsden Hospital, Sulton, UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00499174
• Other Study ID Numbers: PR11; U10CA077202; CAN-NCIC-CTG-PR11; CALGB-140602; SWOG-PR11; CDR0000557348; RTOG-0873; ECOG-JPR.11; ICR-CTSU-ProSTART
• First Posted: Jul 11, 2007
• Last Update Posted: May 12, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NCIC Clinical Trials Group: stage II prostate cancer; adenocarcinoma of the prostate
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Active Surveillance	Radical Intervention
Arm/Group Description	Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression	Radical prostatectomy or radiotherapy based on patient and physician preference conventional surgery: Radical prostatectomy brachytherapy: high dose rate temporary seed implant; permanent seed implant. external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy. Biopsies: Periodic repeat biopsies
Period Title: Overall Study
STARTED	78	102
COMPLETED	0	93
NOT COMPLETED	78	9

Baseline Characteristics

Arm/Group Title	Active Surveillance	Radical Intervention	Total
Arm/Group Description	Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression	Radical prostatectomy or radiotherapy based on patient and physician preference conventional surgery: Radical prostatectomy brachytherapy: high dose rate temporary seed implant; permanent seed implant. external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy. Biopsies: Periodic repeat biopsies	Total of all reporting groups
Overall Participants	78	102	180
Age, Customized (years) [Number]
age group : 40-49	0	2	2
age group : 50-59	9	22	31
age group : 60-69	48	56	104
age group : >= 70	21	20	41
age group : Missing	0	1	1
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	78 100%	102 100%	180 100%
Disease Stage* (participants) [Number]
T1B	1 1.3%	0 0%	1 0.6%
T1C	64 82.1%	79 77.5%	143 79.4%
T2A	12 15.4%	20 19.6%	32 17.8%
T2B	1 1.3%	3 2.9%	4 2.2%
ECOG Performance Status* (participants) [Number]
0	73 93.6%	98 96.1%	171 95%
1	5 6.4%	4 3.9%	9 5%
PSA value (participants) [Number]
< 5. ug/L	43 55.1%	55 53.9%	98 54.4%
>= 5. ug/L	35 44.9%	47 46.1%	82 45.6%
Gleason Score (Combined)* (Count of Participants)
6	78 100%	102 100%	180 100%
Other	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Disease-specific Survival
Description	Time from the date of randomization to the date of death due to prostate cancer.
Time Frame	5 years 6 months

Outcome Measure Data

Analysis Population Description

Due to difficulty in accruing patients to the trial, the trial was closed early, there is no patient died of prostate cancer. Thus, no analysis was done.

Arm/Group Title	Radical Intervention	Active Surveillance
Arm/Group Description	Radical prostatectomy or radiotherapy based on patient and physician preference conventional surgery: Radical prostatectomy brachytherapy: high dose rate temporary seed implant; permanent seed implant. external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy. Biopsies: Periodic repeat biopsies	Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression
Measure Participants	78	102
Median (95% Confidence Interval) [years]	NA	NA

2. Secondary Outcome

Title	Overall Survival
Description	Time from randomization to the date of death due to any causes.
Time Frame	5 years 6 months

Outcome Measure Data

Analysis Population Description

Due to lower patients accrual rate, the trial was closed early with only 3 events reported in the trial, Thus.no formal analysis had been done.

Arm/Group Title	Active Surveillance	Radical Intervention
Arm/Group Description	Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression	Radical prostatectomy or radiotherapy based on patient and physician preference conventional surgery: Radical prostatectomy brachytherapy: high dose rate temporary seed implant; permanent seed implant. external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy. Biopsies: Periodic repeat biopsies
Measure Participants	78	102
Median (95% Confidence Interval) [years]	NA	NA

Adverse Events

Time Frame	q 3 months for 2 years then every 6 months for 5 years and 6 months.
Adverse Event Reporting Description	Adverse events graded according to CTCAE V4.0
Arm/Group Title	Active Surveillance		Radical Intervention
Arm/Group Description	Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression		Radical prostatectomy or radiotherapy based on patient and physician preference conventional surgery: Radical prostatectomy brachytherapy: high dose rate temporary seed implant; permanent seed implant. external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy. Biopsies: Periodic repeat biopsies
All Cause Mortality
	Active Surveillance		Radical Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/78 (1.3%)		2/99 (2%)
Serious Adverse Events
	Active Surveillance		Radical Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/78 (0%)		0/99 (0%)
Other (Not Including Serious) Adverse Events
	Active Surveillance		Radical Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/78 (73.1%)		65/99 (65.7%)
General disorders
Fatigue	15/78 (19.2%)	15	7/99 (7.1%)	7
Pain Testicle	1/78 (1.3%)	1	9/99 (9.1%)	9
Renal and urinary disorders
Incontinence, urinary	3/78 (3.8%)	3	11/99 (11.1%)	11
Urinary frequency	34/78 (43.6%)	34	29/99 (29.3%)	29
Urinary retention	12/78 (15.4%)	12	12/99 (12.1%)	12
Reproductive system and breast disorders
Ejaculatory dysfunction	37/78 (47.4%)	37	41/99 (41.4%)	41

Limitations/Caveats

Due to the early termination of the trial, the small number of patients and the shorter follow up, the reported information may not be reliable.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.