Radiation Therapy in Treating Patients With Relapsed Prostate Cancer After Surgery

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01272050

Collaborator

(none)

350

Enrollment

Locations

Arms

178.8

Anticipated Duration (Months)

12.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known which radiation therapy regimen is more effective in treating patients with relapsed prostate cancer.

PURPOSE: This randomized phase III trial is studying the side effects of radiation therapy and comparing two radiation therapy regimens in treating patients with relapsed prostate cancer after surgery.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

To determine the tumor control in patients with biochemically relapsed prostate cancer without macroscopic disease treated with dose-intensive salvage radiotherapy.
To determine the toxicity in these patients.
To determine the quality of life of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to Gleason score (≥ 8 vs 7 vs ≤ 6), pathological tumor classification (pT3b vs others), lymphadenectomy performed (yes [pN0] vs no [cN0]), persistent PSA after prostatectomy (detectable [≥ 0.1 ng/mL] vs undetectable [< 0.1 ng/mL]), PSA at randomization (> 0.5 ng/mL vs ≤ 0.5 ng/mL), participating center, and radiotherapy technique (3-dimensional conformal radiation therapy [3D-CRT] vs intensity-modulated radiation therapy [IMRT]/rotational techniques). Patient are randomized to 1 of 2 treatment arms.

Arm A: Beginning at least 12 weeks after surgery, patients undergo radiotherapy* once a day, 5 days a week, for 6.4 weeks for a total dose of 64 Gy (in 32 fractions of 2 Gy over 6.4 weeks).
Arm B: Patients undergo radiotherapy* once a day, 5 days a week, for 7 weeks for a total dose of 70 Gy (in 35 fractions of 2 Gy over 7 weeks).

NOTE: *3-dimensional conformal radiation therapy, rotational techniques such as Tomotherapy®, Rapidarc®, or intensity-modulated arc technique and volumetric-modulated arc therapy are all eligible.

Patients complete quality-of-life questionnaires at baseline and at 3, 12, 24, 36, 48, and 60 months after completing study therapy.

After completion of study treatment, patients are followed every 6 months for 3 years and then every 12 months for up to 10 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

350 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose Intensified Salvage Radiotherapy in Biochemically Relapsed Prostate Cancer Without Macroscopic Disease. A Randomized Phase III Trial.

Actual Study Start Date :

Jan 6, 2011

Actual Primary Completion Date :

Jul 29, 2016

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: 64 Gy - Radiation Therapy Arm A: 64 Gy (32 x 2 Gy) without hormonal treatment	Radiation: radiation therapy RT in the standard arm A will be administered to a total dose of 64 Gy in 32 fractions of 2 Gy over 6.4 weeks. RT in the experimental arm B will be administered to a total dose of 70 Gy in 35 fractions of 2 Gy over 7 weeks. Megavoltage equipments with nominal photon energies ≥ 6 MV are required. Rotational techniques such as Tomotherapy®, Rapidarc®, intensity-modulated arc technique (IMAT) and volumetric-modulated arc therapy (VMAT) will also be eligible. The patient will be treated in an isocentric setting and all fields will be applied for 5 days per week for the total RT duration.
Active Comparator: Arm B: 70 Gy - Radiation Therapy Arm B: 70 Gy (35 x 2 Gy) without hormonal treatment	Radiation: radiation therapy RT in the standard arm A will be administered to a total dose of 64 Gy in 32 fractions of 2 Gy over 6.4 weeks. RT in the experimental arm B will be administered to a total dose of 70 Gy in 35 fractions of 2 Gy over 7 weeks. Megavoltage equipments with nominal photon energies ≥ 6 MV are required. Rotational techniques such as Tomotherapy®, Rapidarc®, intensity-modulated arc technique (IMAT) and volumetric-modulated arc therapy (VMAT) will also be eligible. The patient will be treated in an isocentric setting and all fields will be applied for 5 days per week for the total RT duration.

Arm

Intervention/Treatment

Active Comparator: Arm A: 64 Gy - Radiation Therapy

Arm A: 64 Gy (32 x 2 Gy) without hormonal treatment

Radiation: radiation therapy

RT in the standard arm A will be administered to a total dose of 64 Gy in 32 fractions of 2 Gy over 6.4 weeks. RT in the experimental arm B will be administered to a total dose of 70 Gy in 35 fractions of 2 Gy over 7 weeks. Megavoltage equipments with nominal photon energies ≥ 6 MV are required. Rotational techniques such as Tomotherapy®, Rapidarc®, intensity-modulated arc technique (IMAT) and volumetric-modulated arc therapy (VMAT) will also be eligible. The patient will be treated in an isocentric setting and all fields will be applied for 5 days per week for the total RT duration.

Active Comparator: Arm B: 70 Gy - Radiation Therapy

Arm B: 70 Gy (35 x 2 Gy) without hormonal treatment

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Freedom from biochemical progression [from the day of trial randomization to the day of either first recorded biochemical progression, clinical progression or death due to clinical progression up to 10 years.]

Secondary Outcome Measures

Clinical progression-free survival [from the day of randomization to the day of the first record of either local or regional recurrence, distant recurrence, start of hormonal treatment, or death due to any cause up to 10 years.]
Time to hormonal treatment [time from trial randomization to start of hormonal treatment up to 10 years.]
Prostate cancer-specific survival [time from trial randomization to the date of death due to prostate cancer up to 10 years.]
Overall survival [time from trial randomization to the date of death from any cause up to 10 years.]
Acute and late gastrointestinal and genitourinary toxicity according to CTCAE v 4.0 [occurring during treatment and up to 3 months after completion of treatment. Late toxicity is defined as occurring later than 3 months after end of treatment.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of adenocarcinoma of the prostate
Lymph node negative disease
Stage pT2a-3b; R0-1; pN0 or cN0
Undergone a radical prostatectomy ≥ 12 weeks prior to randomization
PSA progression after prostatectomy defined as two consecutive rises with the second rising value > 0.1 ng/mL OR three consecutive rises (the first value must be measured 4 weeks after radical prostatectomy)
PSA ≤ 2 ng/mL at randomization
No persistent PSA > 0.4 ng/mL, 4-20 weeks after radical prostatectomy
No palpable prostatic fossa mass suggestive of recurrence, unless an ultrasound-guided biopsy is non-malignant
No pre-salvage radiotherapy pelvic lymph node enlargement > 1 cm in short axis diameter of the abdomen and pelvis (cN1) (unless the enlarged lymph node is sampled and negative)
No evidence of macroscopic local recurrence or metastatic disease on pre-salvage radiotherapy MRI (with IV contrast) or multislice computed tomography (with IV and oral contrast) of the abdomen and pelvis assessed within 16 weeks prior to randomization
No presence or history of bone metastases (bone scan must be performed in case of clinical suspicion [e.g., bone pain])
Gleason score must be available

PATIENT CHARACTERISTICS:

WHO performance status 0-1
Fertile patients must use effective contraception during and for 6 months after completion of study therapy
Compliant and geographically proximal to allow for proper staging and follow-up
No prior invasive malignancy, except non-melanomatous skin cancer or other malignancies with a documented disease-free survival of ≥ 5 years
No bilateral hip prosthesis
No severe or active co-morbidity likely to impact on the advisability of dose-intensive salvage radiotherapy, including any of the following:
History of inflammatory bowel disease
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
Transmural myocardial infarction within the past 6 months
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomization
No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or filling out quality-of-life questionnaires

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior pelvic radiotherapy
No hormonal treatment or bilateral orchiectomy prior to or following prostatectomy
At least 4 weeks since prior and no concurrent use of products known to affect PSA levels (e.g., PC Calm, PC Plus, PC SPES, finasteride, or fluconazole)
At least 30 days since prior treatment in another clinical trial
No other concurrent anticancer treatments, including luteinizing hormone-releasing hormone (LHRH) analogues, antiandrogens, orchiectomy, or chemotherapy
No other concurrent investigational or experimental treatments or drugs

INCLUSION CRITERIA

Patient must give written informed consent before randomization.
Lymph node negative adenocarcinoma of the prostate treated with radical prostatectomy at least 12 weeks before randomization. Tumor stage pT2a-3b, R0-1, pN0 or cN0 according to the UICC TNM 2009 (see Appendix 1), Gleason score available.
PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises. The first value must be measured earliest 4 weeks after radical prostatectomy.
PSA at randomization ≤ 2 ng/mL.
WHO performance status 0-1 at randomization.
Age at randomization between 18 and 75 years.
Baseline QoL questionnaire (QLQ) has been completed.
Patient agrees not to father a child during salvage RT and during 6 months thereafter.
Patient compliance and geographic proximity allow proper staging and follow-up.
The responsible pathologist has agreed to provide sample material for central pathological review (see Section 16) and tissue banking (only if patient gave informed consent) within the specified timelines.

EXCLUSION CRITERIA

Persistent PSA 4-20 weeks after radical prostatectomy > 0.4 ng/mL
Palpable prostatic fossa mass suggestive of recurrence, unless an ultrasound guided biopsy is non-malignant.
Pre-salvage RT pelvic lymph node enlargement > 1 cm in short axis diameter of the abdomen and pelvis (cN1), unless the enlarged lymph node is sampled and negative, and/or evidence of macroscopic local recurrence or metastatic disease on pre-salvage RT MRI (magnetic resonance imaging; with i.v. contrast) or multislice computed tomography (CT; with i.v. and oral contrast) of the abdomen and pelvis assessed within 16 weeks prior to randomization.
Presence or history of bone metastases. Bone scan must be performed in case of clinical suspicion (e.g. bone pain).
Prior invasive malignancy, except non-melanomatous skin cancer or other malignancies with a documented disease-free survival for a minimum of 5 years.
Hormonal treatment or bilateral orchiectomy prior to or following prostatectomy.
Bilateral hip prosthesis.
Prior pelvic radiotherapy.
The use of products known to affect PSA levels within 4 weeks prior to start of trial treatment (e.g. PC Calm, PC Plus, PC SPES, finasteride, fluconazole).
Severe or active co-morbidity likely to impact on the advisability of dose intensified salvage RT.
Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent or filling out QoL questionnaires.
Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen	Belgium	2020
2	Ghent University Hospital	Ghent	Belgium	9000
3	St. Lukas Hospital Ghent	Ghent	Belgium	9000
4	Universitaetsklinikum Aachen, Klinik für Strahlentherapie	Aachen	Germany	52074
5	Charite University Hospital - Campus Virchow Klinikum	Berlin	Germany	13353
6	University Hospital and Medical Faculty Technical University of Dresden	Dresden	Germany	D-01307
7	Universitaetsklinikum Essen, Klinik für Strahlentherapie	Essen	Germany	45147
8	Universitätsklinikum Saarland	Homburg	Germany	66421
9	Klinikum der LMU Muenchen	Munich	Germany	D-81377
10	Technische Universitaet Muenchen	Munich	Germany	D-81675
11	Klinikum der Universitaet Regensburg	Regensburg	Germany	93051
12	Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock	Rostock	Germany	18059
13	Universitaet Tuebingen	Tuebingen	Germany	72076
14	Klinik fuer Strahlentherapie Universitaet Wuerzburg	Wuerzburg	Germany	97080
15	Kantonsspital Aarau	Aarau	Switzerland	5001
16	Universitaetsspital-Basel	Basel	Switzerland	CH-4031
17	Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli	Bellinzona	Switzerland	6500
18	Inselspital Bern	Bern	Switzerland	3010
19	Radio-Onkologiezentrum Biel-Seeland-Berner Jura AG	Biel	Switzerland	2503
20	Kantonsspital Graubuenden	Chur	Switzerland	7000
21	Kantonsspital Luzern	Luzern	Switzerland	6000
22	Kantonsspital Muensterlingen	Münsterlingen	Switzerland	8596
23	Hopital de Sion	Sion	Switzerland	1951
24	Kantonsspital - St. Gallen	St. Gallen	Switzerland	9007
25	Radio-Onkologie Berner Oberland AG	Thun	Switzerland	3600
26	Klinik Hirslanden	Zurich	Switzerland	8032
27	City Hospital Triemli	Zurich	Switzerland	8063
28	UniversitaetsSpital Zuerich	Zurich	Switzerland	8091