Image-guided focal dose escalation in patients with primary prostate cancer treated with primary external beam hypofractionated radiation therapy (HypoFocal) – a prospective, multicenter, randomized phase III study.
Organizational Data
- DRKS-ID:
- DRKS00022915
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2022-07-21
- Last update in DRKS:
- 2024-02-13
- Registration type:
- Prospective
Acronym/abbreviation of the study
HypoFocal-SBRT
URL of the study
No Entry
Brief summary in lay language
One of the principles of radiotherapy is to deliver the highest possible dose of radiation to the diseased tissue and to spare the healthy surrounding tissue as much as possible. A type of radiotherapy that has been well investigated in several studies and is recommended and frequently performed according to international guidelines is the so-called "moderate hypofractionated radiotherapy", also known as MHRT. In this well-established radiation therapy for patients with newly diagnosed prostate cancer, the entire prostate is treated with a uniform dose of radiation. Because the prostate is adjacent to the urinary bladder and rectum, the radiation dose to the entire prostate cannot be increased arbitrarily without risking increased side effects to the bladder and rectum. New diagnostic techniques such as magnetic resonance imaging (MRI) and PSMA PET/CT (prostate specific membrane antigen positron emission tomography/computed tomography) allow very accurate imaging of the tumor mass in the prostate. This study will compare two different radiation options, study arm A and study arm B. In study arm B, patients will be treated with the above mentioned MHRT: The irradiation dose is distributed homogeneously/uniformly over the entire prostate in 20 irradiation sessions over a period of 4 weeks. The irradiation dose to the organs at risk (normal, surrounding tissue) follows strict guidelines. In study arm A, a higher irradiation dose is given to the tumor areas in the prostate than to the rest of the prostate (hereafter referred to as focused irradiation). For the surrounding normal tissues such as the rectum and bladder, very strict dose constraints for the organs at risk must also be met. At the same time, in study arm A, the number of treatments is reduced to 5, which take place within 3 weeks. This is possible because a higher radiation dose per radiation session is delivered specifically to the prostate and tumor. This procedure is called stereotactic fractionated radiosurgery.
Brief summary in scientific language
The individualization of radiotherapy (RT) based on modern medical imaging in terms of focal radiation dose escalation on intraprostatic tumors with stereotactic body radiotherapy (SBRT) will increase the relapse free survival (RFS) in patients with primary prostate cancer (PCa) compared to moderate hypofractionated radiotherapy (MHRT). A reduction in treatment time (5 versus 20 RT fractions) will further increase the patients’ convenience.
Health condition or problem studied
- Free text:
- Prostate Cancer
- Healthy volunteers:
- No
Interventions, Observational Groups
- Arm 1:
- RT prostate: 35 Gy in 7 Gy per fraction RT seminal vesicles: 30 Gy in 6 Gy per fraction RT on the intraprostatic tumour mass (ITM): 40 – 42 Gy in 8 - 8.4 Gy per fraction. If the boost volume is ≥10 ml and/ or ≥ 1/3 of the prostate, the dose on the ITM has to be restrained to 40 Gy in 8 Gy per fraction. The dose escalation has to be performed by keeping the strict dose constraints for the organs at risk. Technique: IMRT/IGRT/SBRT/SIB Duration: 5 fractions, 3 week
- Arm 2:
- RT prostate: 60-62 Gy in 3-3.1 Gy per fraction RT seminal vesicles: 46.4 Gy in 2.32 Gy per fraction in 5 fractions per week Technique: IMRT/IGRT/SIB Duration: 20 fractions, 4 weeks.
Endpoints
- Primary outcome:
- Primary endpoint is relapse free survival (RFS), defined as time from randomization to relapse or death. Relapse free survival times will be censored at the time seen last alive without relapse. For the definition of relapse see 2.3.1.
- Secondary outcome:
- - Time to local failure; after randomization. Local recurrences have to be confirmed by biopsy. - Metastatic free survival after randomization, (all metastases have to be confirmed by imaging, preferably by PSMA-PET/CT or mpMR imaging) - Overall (OS) and prostate cancer specific (PCSS) survival after randomization - Time to biochemical failure after randomization (phoenix definition) - Patient reported acute quality of life after treatment, at month 3 and month 6 after randomization (QOL: EPIC-26 and IPSS) - Patient reported late quality of life at months 9,12,15,18 21, 24, 30, 36, 42, 48 and months 54, 60, 66, 72, 78, 84 up to 90 after randomization (QOL: EPIC-26 and IPSS) - Cumulative acute genitourinary (GU) and gastrointestinal (GI) toxicities during and up to 3 months after RT using the CTCAEv5.0 criteria - Cumulative chronic GU and GI toxicities after RT using the CTCAEv5.0 criteria - Feasibility and adherence to dose constraints by measuring the ratio between: patients with fulfilled dose constraints and prescription doses / recruited patients - Characterization of safety: adverse events - Translational side projects include: assessment of immune response, multidimensional biomarkers for risk prediction, comparison and evaluation of PSMA-PET and mpMRI in treatment planning for PCa patients including artificial intelligence tools for automated image interpretation, strategies for patients’ empowerment and involvement (all side projects are defined in separate protocols of the clinical part of the HypoFocal-SBRT study)
Study Design
- Purpose:
- Treatment
- Allocation:
- Randomized controlled study
- Control:
-
- Active control (effective treatment of control group)
- Phase:
- III
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Parallel
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Austria
- Cyprus
- Germany
- Switzerland
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- University medical center Klinik für Strahlenheilkunde Freiburg im Breisgau
- Medical center MEDICLIN Robert Janker Klinik - Klinik für Strahlenheilkunde und Radioonkologie Bonn
- Other Radiologische Allianz Hamburg
- University medical center Technische Universität Dresden - Medizinische Fakultät - Klinik und Poliklinik für Strahlentherapie Dresden
- University medical center Universitätsklinikum Tübingen - Universitätsklinik für Radioonkologie Tübingen
- University medical center Universitätsklinikum Ulm - Strahlentherapie und Radioonkologie Ulm
- Medical center German Oncology Center Agios Athanasios, Limassol, Zypern
- Medical center Ortenau Klinikum Offenburg-Kehl - MVZ Offenburg Offenburg
Recruitment period and number of participants
- Planned study start date:
- 2022-09-01
- Actual study start date:
- 2022-08-23
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 374
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- Male
- Minimum Age:
- 18 Years
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- 1. Histologically confirmed adenocarcinoma of the prostate (histological confirmation can be based on tissue taken at any time, but a re-biopsy should be considered if the biopsy is more than 12 months old) 2. Primary localized PCa (cN0 and cM0 in mpMRI and PSMA-PET): - high- or very high-risk according to NCCN v2.2021 (see 20.3) OR - unfavorable intermediate-risk disease according to NCCN v2.2021 (see 20.3) 3. Signed written informed consent for this study 4. Age >18 years 5. Previously conducted PSMA-PET/CT and mpMRI scans or PSMA-PET/MR, fulfilling standard requirements for PCa (see also 6.5) 6. ECOG Performance score 0 or 1 7. IPSS Score ≤15 8. Prostate volume ≤ 75 ml at RT planning
Exclusion Criteria
1. Evidence of neuroendocrine tumor cells 2. Prior radiotherapy to the prostate or pelvis 3. Prior radical prostatectomy 4. Prior focal therapy approaches to the prostate 5. Time gap between the beginning of ADT and conduction of mpMRI and PSMA-PET scans is >1 month 6. Radiologically suspicious or pathologically confirmed lymph node involvement (cN+) in mpMRI and/or PSMA-PET/CT 7. Evidence of metastatic disease (cM+) in mpMRI and/or PSMA-PET/CT 8. Evidence of cT4 disease in mpMRI and/or PSMA-PET/CT 9. PSA >30 ng/ml prior to starting ADT 10. Expected patient survival <5 years 11. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts 12. Contraindication to undergo a mpMRI scan 13. Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery (TURP or HOLEP) within the last 6 months prior to randomization 14. Medical conditions likely to make radiotherapy inadvisable e.g. acute inflammatory bowel disease, hemiplegia or paraplegia 15. Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival 16. Any other contraindication to external beam radiotherapy (EBRT) to the pelvis 17. In mpMRI and PSMA-PET/CT or PSMA-PET/MRI scans no visible tumor 18. Participation in any other interventional clinical trial within the last 30 days before the start of this trial 19. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed 20. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial; 21. Known or persistent abuse of medication, drugs or alcohol 22. Patients expected to have severe set up problems 23. Dose constraints for organs at risk cannot be adhered to
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum FreiburgBreisacher Straße 15379110 FreiburgGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum Freiburg Klinik für StrahlenheilkundeProf. Dr. med. Anca-Ligia GrosuRobert-Koch-Str. 379106 FreiburgGermany
- Telephone:
- 0049 761 270 94600
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Universitätsklinikum Freiburg Klinik für StrahlenheilkundeDr. med. Simon SpohnRobert-Koch-Straße 379106 FreiburgGermany
- Telephone:
- 0049 761 270 94010
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Universitätsklinikum Freiburg Klinik für StrahlenheilkundeProf. Dr. med. Anca-Ligia GrosuRobert-Koch-Str. 379106 FreiburgGermany
- Telephone:
- 0049 761 270 94600
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesministerium für Bildung und Forschung Dienstsitz Bonn Förderkennzeichen: 01KD2201Heinemannstr. 253175 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bmbf.de
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission der Albert-Ludwigs-Universität FreiburgEngelberger Str. 2179106 FreiburgGermany
- Telephone:
- +49-761-27072600
- Fax:
- +49-761-27072630
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2021-03-05
- Ethics committee number:
- 21-1183
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2021-04-22
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry