Radiation Therapy in Treating Patients With Relapsed Prostate Cancer After Surgery

NCT ID: NCT01272050

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-06
• Study Completion Date: 2024-05-31

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: 64 Gy - Radiation Therapy

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

Group Type: ACTIVE_COMPARATOR

radiation therapy

Intervention Type: RADIATION

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 B: 70 Gy - Radiation Therapy

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

Group Type: ACTIVE_COMPARATOR

radiation therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pirus Ghadjar, MD

Role: STUDY_CHAIR

Charite University, Berlin, Germany

Daniel M. Aebersold, Prof.

Role: STUDY_CHAIR

Bern University Hospital

George N. Thalmann, Prof.

Role: STUDY_CHAIR

Bern University Hospital

Daniel Zwahlen, PD Dr.

Role: STUDY_CHAIR

Kantonsspital Graubünden

Locations

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Ghent University Hospital

Ghent, , Belgium

St. Lukas Hospital Ghent

Ghent, , Belgium

Universitaetsklinikum Aachen, Klinik für Strahlentherapie

Aachen, , Germany

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

University Hospital and Medical Faculty Technical University of Dresden

Dresden, , Germany

Universitaetsklinikum Essen, Klinik für Strahlentherapie

Essen, , Germany

Universitätsklinikum Saarland

Homburg, , Germany

Klinikum der LMU Muenchen

Munich, , Germany

Technische Universitaet Muenchen

Munich, , Germany

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock

Rostock, , Germany

Universitaet Tuebingen

Tübingen, , Germany

Klinik fuer Strahlentherapie Universitaet Wuerzburg

Würzburg, , Germany

Kantonsspital Aarau

Aarau, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Radio-Onkologiezentrum Biel-Seeland-Berner Jura AG

Biel, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Kantonsspital Luzern

Lucerne, , Switzerland

Kantonsspital Muensterlingen

Münsterlingen, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopital de Sion

Sion, , Switzerland

Radio-Onkologie Berner Oberland AG

Thun, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Belgium; Germany; Switzerland

References

Zwahlen DR, Schroder C, Holer L, Bernhard J, Holscher T, Arnold W, Polat B, Hildebrandt G, Muller AC, Martin Putora P, Papachristofilou A, Schar C, Hayoz S, Sumila M, Zaugg K, Guckenberger M, Ost P, Giovanni Bosetti D, Reuter C, Gomez S, Khanfir K, Beck M, Thalmann GN, Aebersold DM, Ghadjar P. Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial. Clin Transl Radiat Oncol. 2024 Apr 25;47:100786. doi: 10.1016/j.ctro.2024.100786. eCollection 2024 Jul.

Reference Type: DERIVED

PMID: 38706726 (View on PubMed)

Beck M, Sassowsky M, Schar S, Mathier E, Halter M, Zwahlen DR, Holscher T, Arnold W, Polat B, Hildebrandt G, Muller AC, Putora PM, Papachristofilou A, Hayoz S, Schar C, Li Q, Sumila M, Zaugg K, Guckenberger M, Ost P, Bosetti DG, Reuter C, Gomez S, Khanfir K, Aebersold DM, Ghadjar P, Pra AD. Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial. Int J Radiat Oncol Biol Phys. 2022 May 1;113(1):80-91. doi: 10.1016/j.ijrobp.2021.12.174. Epub 2022 Jan 3.

Reference Type: DERIVED

PMID: 34990777 (View on PubMed)

Ghadjar P, Hayoz S, Bernhard J, Zwahlen DR, Holscher T, Gut P, Polat B, Hildebrandt G, Muller AC, Plasswilm L, Papachristofilou A, Schar C, Sumila M, Zaugg K, Guckenberger M, Ost P, Reuter C, Bosetti DG, Khanfir K, Gomez S, Wust P, Thalmann GN, Aebersold DM; Swiss Group for Clinical Cancer Research (SAKK). Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial. Eur Urol. 2021 Sep;80(3):306-315. doi: 10.1016/j.eururo.2021.05.033. Epub 2021 Jun 14.

Reference Type: DERIVED

PMID: 34140144 (View on PubMed)

Ghadjar P, Hayoz S, Bernhard J, Zwahlen DR, Holscher T, Gut P, Guckenberger M, Hildebrandt G, Muller AC, Plasswilm L, Papachristofilou A, Stalder L, Biaggi-Rudolf C, Sumila M, Kranzbuhler H, Najafi Y, Ost P, Azinwi NC, Reuter C, Bodis S, Kaouthar K, Wust P, Thalmann GN, Aebersold DM. Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10. J Clin Oncol. 2015 Dec 10;33(35):4158-66. doi: 10.1200/JCO.2015.63.3529. Epub 2015 Nov 2.

Reference Type: DERIVED

PMID: 26527774 (View on PubMed)

Other Identifiers

SWS-SAKK-09/10

Identifier Type: -

Identifier Source: secondary_id

EU-21088

Identifier Type: -

Identifier Source: secondary_id

CDR0000691926

Identifier Type: OTHER

Identifier Source: secondary_id

SAKK 09/10

Identifier Type: -

Identifier Source: org_study_id